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  • 101
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 123 (1996), S. 280-288 
    ISSN: 1432-2072
    Keywords: Ventral pallidum ; Self-stimulation ; Dopamine ; Dopamine antagonists ; 7-OH-DPAT ; Cocaine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study examines the role of dopaminergic neurotransmission in modulating the reinforcing effect of ventral pallidum (VP) intracranial self-stimulation (ICSS). Fifty four adult rats were implanted with a monopolar moveable stimulating electrode in the VP. Rate-frequency functions were determined by logarithmically decreasing the number of pulses in a stimulation train from a value that sustained maximal responding to one that did not sustain responding. After the ICSS thresholds stabilized, the animals received treatments with several doses of cocaine and of various selective drugs acting at the level of DA receptor subtypes. Their effects on threshold and asymptotic rate were analyzed. Cocaine produced a significant decrease in ICSS threshold but had no significant effect on the asymptotic rate. A significant decrease in ICSS threshold was also seen with the D3 agonist 7-OH-DPAT. This was associated with a decrease rather than an increase in performance. D1 and D2DA receptor blockers (haloperidol, SCH-23390, raclopride and sulpiride) produced a dose dependent increase in ICSS threshold and a decrease in the maximal rate. The results suggest that DA plays a modulatory role in VP intracranial self-stimulation, and that D1, D2 and D3 receptors are involved in the mediation of this effect, although to different extents.
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  • 102
    ISSN: 1432-2072
    Keywords: Cannabinoids ; Pigeon ; SR141716A ; Drug discrimination ; Startle ; Fixed consecutive number ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract SR141716A (Sanofi Recherche), a pyrazole derivative with high affinity for rat and human CB1 cannabinoid receptors, has recently been reported to reverse biochemical, physiological and behavioral effects induced by cannabinoid agonists. The present experiments characterized the activity of SR141716A (SR) in behavioral procedures designed to assess its antagonistic and intrinsic effects on unconditioned behavior and on complex learned behaviors. Six adult male pigeons were trained to discriminate injections of 0.56 mg/kg Δ9-tetrahydrocannabinol (Δ9-THC) from vehicle under a two-key, fixed-ratio schedule of food reinforcement. SR (IM) produced a nearly complete blockade of THC-appropriate responding occasioned by the training dose without inducing significant changes in session response rates, but also produced partial substitution for Δ9-THC when administered alone. In another group of pigeons trained under a multiple schedule of signaled and unsignaled fixed consecutive number (FCN) responding, SR had little effect on accuracy, but Δ9-THC produced dose-related decreases in accuracy under both schedule components. SR was also evaluated in acoustic startle procedures in rats. SR produced little effect either on startle amplitude or prepulse inhibition of acoustic startle. In contrast, the potent cannabinomimetic CP-55, 940 produced large decreases in startle responses elicited by 120 dB [A] broad-band noise. These decreases were completely reversed by SR (10 mg/kg, IP). In concurrent measures, SR blocked the hypothermic effect CP-55,940. These results suggest that SR is an effective antagonist of the psychoactive effects of cannabinoids.
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  • 103
    ISSN: 1432-2072
    Keywords: Maternal separation ; Conditioned incentive stimuli ; Conditioned locomotor activity ; Mesolimbic dopamine ; Amphetamine ; Sulpiride ; SCH 23390 ; Clonidine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Adult hooded rats exposed to a repeated maternal separation procedure during the neonatal period showed a blunted expression of locomotor hyperactivity conditioned to the presentation of the daily food ration. We have demonstrated that the expression of food-conditioned anticipatory hyperactivity is sensitive to the response-enhancing effects of systemicd-amphetamine (0.5; 1.0 mg/kg) and to the response-attenuating effects of the selective dopamine D2 antagonist sulpiride (8; 20 mg/kg), the selective dopamine D1 antagonist SCH 23390 (0.01; 0.022 mg/kg) and the mixed α1/α2 adrenoceptor agonist clonidine (5; 15 μg/kg) in a dose dependent manner. Animals from the early separation groups showed a reduced enhancement of activity in response to 0.5 mg/kgd-amphetamine and a greater attenuation of activity in response to 8 mg/kg sulpiride and 5 μg/kg clonidine. Female separated rats also exhibited an attenuated locomotor response to the unconditioned stimulant effects of 0.5 mg/kg systemicd-amphetamine. The experiments confirm that early maternal separation attenuates the response to conditioned appetitive cues in adult rats and implicate altered dopaminergic and noradrenergic function in the changes. It is possible that early maternal separation in the rat may offer a useful preparation for investigation of the neural substrates mediating affective development and affective psychopathology.
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  • 104
    ISSN: 1432-2072
    Keywords: Environmental conditioning ; Nicotine ; Rat ; Sensitization ; Behavioral and neurochemical analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have investigated the effects of environmental conditioning on the induction of nicotine sensitization of locomotion, stereotypy and nucleus accumbens dopamine release. Sprague-Dawley rats, some of which had been previously implanted with a microdialysis guide cannula over the nucleus accumbens, were sensitized with 5 days of repeated nicotine (0.6 mg/kg per day, SC) or saline injections (1 ml/kg per day). During nicotine treatment the drug administration was either paired with the microdialysis/activity monitor testing chamber (conditioned) (n=6) or with the animal's home cage (unconditioned) (n=6) and after 60 min the animal was returned to home cage and received a second injection of saline 15 min later. A third group received saline in the testing apparatus followed by nicotine in the home cage (pseudo-conditioned) (n=6). In the guide cannulated animals, 2 mm microdialysis probes were inserted after completing day 5 of treatment and all animals were tested for their response to nicotine (0.6 mg/kg, SC) on day 6. Both locomotor activity and nucleus accumbens dopamine release showed a larger response subsequent to nicotine challenge in the nicotine versus saline pretreated animals in the conditioned group, but not in the unconditioned group. In the pseudo-conditioned group there was an increase in the stereotypy responses to nicotine, however the locomotor and dopamine release responses were not significantly enhanced. The results from the conditioned group were confirmed in animals which were tested for behavioral activation and dopamine release simultaneously (n=5). These findings indicate that nicotine sensitization of locomotor activity and nucleus accumbens dopamine release (using a 5-day pretreatment protocol) is dependent on conditioning the animal to the testing environment during nicotine pretreatment.
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  • 105
    ISSN: 1432-2072
    Keywords: Thyrotrophin-releasing hormone ; RX77368 ; Alzheimer's disease ; AMPA ; Septal-hippocampal ; Working memory ; Delayed non-matching to position (DNMTP) ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of the present study was to determine the effect of a thyrotrophin-releasing hormone (TRH) analogue, RX77368, on performance of a working memory test, using a delayed non-matching to position (DNMTP) procedure, in (RS)-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-induced septal-hippocampal lesioned rats. Following a postsurgery recovery period, pretrained rats were tested once daily on DNMTP, 30 min post-administration of RX77368 (1.0 mg kg−1, IP) or saline. AMPA-induced lesions significantly reduced percent correct responses during the second week of testing. Comparison of percent correct responses between days 1 and 13 of testing showed that sham rats significantly improved DNMTP performance, whereas lesioned rats did not. RX77368 significantly reduced general locomotor activity in sham rats in activity boxes, but did not disrupt non-mnemonic measures, such as locomotion and motivation, in the DNMTP test. RX77368 increased percent correct responses in AMPA-lesioned rats on days 8–10 and 11–13. There was also a significant improvement in percent correct responses achieved between day 1 and 13 in RX77368-treated lesioned and sham rats. These results showed that: (i) septal-hippocampal lesioned rats did not improve over the testing period; and (ii) on test days when a significant impairment was present, RX77368 partially improved DNMTP performance.
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  • 106
    ISSN: 1432-2072
    Keywords: Benzodiazepines ; BZ-1 (ω 1) receptor ; Anxiety ; Elevated plus-maze ; Risk assessment ; Locomotor activity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The behavioral effects of a wide range of BZ (ω) receptor ligands, including non-selective full (alprazolam, clorazepate, chlordiazepoxide and diazepam) and partial (bretazenil, imidazenil and Ro 19-8022) agonists, and selective BZ-1 (ω 1) (abecarnil, CL 218,872, CL 284,846 and zolpidem) receptor ligands, were compared in the rat elevated plus-maze test. Behaviors recorded comprised the traditional indices of anxiety as well as a number of ethologically derived measures. In addition, the specificity of drug effects was evaluated by measuring spontaneous locomotor activity in activity cages in separate groups of animals. Results showed that all compounds tested not only increased the proportion of time spent and proportion of entries into the open arms of the maze (considered as traditional indices of anxiety) but also affected headdippings and attempts at entry into open arms, which can be considered as indices of risk assessment responses. However, the magnitude of these effects was generally smaller with the BZ-1 (ω 1) selective agents. Moreover, additional differences were apparent on the total number of arm entries measure, which was significantly increased by most full and all partial agonists, but was unaffected by the selective BZ-1 (ω 1) compounds. If it is assumed that total arm entries are contaminated by anxiety, the latter finding indicates a weaker anxiety-reducing potential of selective BZ-1 (ω 1) ligands. Importantly, the increase in total arm entries induced by the non-selective agents was not associated with a similar effect on locomotion as revealed in the actimeter. Finally, anxiolysis produced by the BZ-1 (ω 1) ligands was invariably observed at doses which reduced locomotor activity, suggesting that the anxiolytic-like effects of these compounds are confounded by decreases in locomotor activity.
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  • 107
    ISSN: 1432-2072
    Keywords: Antidepressants ; Desipramine ; Fluvoxamine ; Timing ; Fixed-interval peak procedure ; Interval bisection task ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Acute treatment with antidepressant drugs is known to increase the mean interresponse time (IRT) in the IRT 〉72-s schedule of reinforcement. In order to examine the possibility that this effect may reflect an action of the antidepressants on timing processes, we tested the effects of two antidepressants, desipramine and fluvoxamine, on behaviour maintained under two other timing schedules in rats. In the fixed-interval peak procedure (fixed-interval 30-s), acute treatment with desipramine (8 mg kg−1) reduced response rate, whereas acute treatment with fluvoxamine (8 mg kg−1) increased it. Neither drug significantly altered the time to attainment of peak response rate or the Weber fraction. In the interval bisection task (standard durations 2 s and 8 s), the bisection point was not significantly altered by acute treatment with either drug. Chronic treatment with desipramine (8 mg kg−1 b.d.) had no effect on any of the indices of timing under either schedule. Chronic treatment with fluvoxamine (8 mg kg−1 b.d.) reduced the time to attainment of peak response rate but had no effect on the Weber fraction under the fixed-interval peak procedure, and did not alter the bisection point or Weber fraction under the interval bisection procedure. The failure of desipramine and fluvoxamine to increase the time to peak response rate or the bisection point at doses that significantly altered operant response rate suggests that the effect of these drugs on IRT schedule performance is unlikely to reflect an interaction with timing processes.
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  • 108
    ISSN: 1432-1106
    Keywords: Hippocampus ; Temperature ; Granule cell ; Exploration ; Fascia dentata ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Brain temperature changes accompany exploratory behavior and profoundly affect field potential amplitudes recorded in hippocampus. The waveform alterations in fascia dentata include a reduction in population spike area, which might be explained by fewer granule cells firing in response to a given stimulus or by an alteration in the size or shape of the individual action potentials. This study was designed to assess these alternate possibilities. In experiment 1, changes in the shape and firing rates of single cells recorded in the fascia dentata of awake rats were compared with changes in the population spike before and after a bout of activity. Single-unit amplitudes were significantly reduced following exploration, and there was a small (〈 3%) change in unit spike-width. These changes, however, were insufficient to account, in a linear fashion, for the entire decline in the population spike. In experiment 2, radiant heat was used to manipulate brain temperature in anesthetized rats. As in the first experiment, the magnitude of change in the extracellular units was much smaller than the change in population spike amplitude. The spontaneous firing rates of the cells were also modified by brain temperature changes. In experiment 3, the polysynaptic, contralateral commissural response (which covaries with changes in the ipsilateral population spike at a fixed temperature) was measured as a function of either exploratory behavior or radiant heat. The relationship between the ipsilateral population spike and corresponding polysynaptic commissural response was altered following exploration and passive warming in a manner consistent with a reduction in net granule cell output, reduced transmission efficacy through the polysynaptic circuit, or a combination of these. Taken together these data suggest that at least two factors contribute to temperature-dependent changes in the perforant path-evoked population spikes recorded in the fascia dentata: changes in the size of individual action potentials and alterations in discharge of action potentials in response to a given stimulus.
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  • 109
    ISSN: 1432-1106
    Keywords: Barrel field ; Barrels ; Forepaw ; Mapping ; Cytochrome oxidase ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The physiological representation of the forepaw in rat primary somatosensory cortex (SI) is topographically organized. This representation is associated with the unique arrangement of barrels in layer IV of the forepaw barrel subfield (FBS) in SI and provides an example of a relationship between cortical structure and function. It has been reported that removal of peripheral afferent input to the FBS prior to postnatal day 5 or 6 results in a disorganized FBS, while deafferentation at later times produces little or no alteration of the FBS. Therefore, restricted deafferentations of individual digits in adult rats should result in little, if any, disruption of the FBS, while at the same time eliminating afferent input to the FBS from a localized region of the periphery. This manipulation is likely to create a mismatch between structure and function and offer insight into what barrels actually represent in the adult deafferent. In the present study, we amputated digit three (D3) in eight adult rats, allowed a 1-month survival time, physiologically mapped the representation of D2, D4, and the stump, and compared this physiological map to the underlying barrels in the FBS. Our results showed that FBS barrels formerly associated with the representation of D3 were now associated with the representation of surrounding digits D2 and D4, as well as the remaining stump. By superimposing the morphological and physiological map upon one another, it was clear that the D2 and D4 representations expanded into the former D3 barrel territory and septae between the barrels. The reorganized physiological map was somatotopically organized, even though the general configuration of the morphological map remained unaltered, as visualized with cytochrome oxidase staining. These results suggest that in the deafferent, neurons within FBS barrels previously associated with the representation of punctate regions of skin become associated with neighboring regions of skin. A morphological substrate to account for this cortical reorganization is described.
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  • 110
    ISSN: 1432-1106
    Keywords: Synapsin I, II ; In situ hybridization ; Northern blot ; Gene expression ; Postnatal brain development ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Synapsin Ia, Ib, IIa, and IIb are neuronal phosphoproteins, which are supposed to play a role in the short-term regulation of neurotransmitter release. Besides a high degree of homology among the four synapsin subtypes, there are structural differences in the 3′end of their coding region. Here we present the first extensive study of the expression of their gene transcripts by using in situ hybridization and northern blot analysis. Our results show regionally and temporally distinct expression patterns of synapsin Ia, Ib, IIa, and IIb, which suggests different functional properties of the four synapsin subtypes. There was no specific messenger RNA (mRNA) expression of synapsin IIb in most brain regions apart from the cerebellum, suggesting a minor functional role of this synapsin subtype. Synapsin Ia, Ib, and IIa mRNA were expressed earlier in ontogenetically older brain regions such as the piriform cortex, the thalamus, and the hippocampus and later in ontogenetically younger areas such as the neocortex and the cerebellum. Owing to the distinct expression pattern of the synapsin subtypes, we suppose that the synapsins might be essential for the underlying molecular mechanism of pattern formation and plasticity in distinct brain regions during different states of rat brain development.
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  • 111
    ISSN: 1432-1106
    Keywords: Ornithine decarboxylase ; Polyamines ; Brain development ; Neurochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Pregnant rats were treated for five consecutive days during gestation with s.c. injections of the ornithine decarboxylase (ODC) inhibitor alpha-difluoromethylornithine (DFMO). Treatment beginning at gestational days 13 or 14 was effective in inhibiting ODC and altering polyamine levels, and resulted in relatively small decreases in body and forebrain weight, but not in significant differences in adult neurochemistry. Neonatal rats were treated with DFMO from postnatal day 0 (PD 0) to PD 24. In addition to some somatic effects (decreased body weight, delayed eyelid opening and delayed fur growth) the postnatal treatment resulted in a permanent decrease in brain weight, which was mainly due to a dramatic decrease in cerebellar size. During treatment, and 3 days after the end of it, the levels of putrescine and spermidine, but not those of spermine, were consistently lower in the cerebellum and forebrain of DFMO-treated rats than in controls. On the other hand, ODC appeared strongly inhibited only during the first phase of the treatment and showed recovery, and also rebound of the activity, during the second part of the treatment. A screening of neurochemical markers related to cholinergic, GABAergic and glutamatergic neurons, as well to astrocytes and oligodendrocytes was performed in several brain regions (cerebellum, olfactory bulbs, cortex, striaturn, hippocampus) of some of these rats once they became adults. Significant alterations for all the parameters tested, with the exception of the marker for the glutamatergic transmission, were measured in the undersized cerebellum of the neonatally DFMO-treated rats. A shorter neonatal treatment with DFMO (from PD 1 to 6) resulted, in the adult, in decreased cerebellar size and in neurochemical alterations, both very similar to those occurring after the prolonged treatment. In the other brain regions a few minor differences were noticed. The present results show that: (1) the brain polyamine system is differently regulated in foetuses with respect to newborns; (2) the effects of chronic ODC blockade are different on prenatally or postnatally proliferating neurons, due either to a lower sensitivity of gestation ally proliferating neurons or to a subsequent recovery; and (3) chronic postnatal ODC inhibition has a strong effect on proliferating neurons, but little effect on further maturation of postmitotic neurons.
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  • 112
    ISSN: 1432-1106
    Keywords: Entorhinal cortex ; Claustrum ; Presubiculum ; Epilepsy ; Neurodegeneration ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Neurons in layer III of the medial entorhinal area (MEA) in the rat are extremely vulnerable to local injections of amino-oxyacetic acid and to exprimentally induced limbic seizures. A comparable specific pathology has been noted in surgical specimens from patients with temporal lobe epilepsy. Efforts to understand this preferential neuronal vulnerability led us to study the neural input to this layer in the rat. Iontophoretic injection of the retrograde tracer fast blue, aimed at layer III of the MEA, resulted in retrogradely labeled neurons in the presubiculum in all the injected hemispheres. The nucleus reuniens thalami, the anteromedial thalamic nucleus, the ventral portion of the claustrum (endopiriform nucleus), the dorsomedial parts of the anteroventral thalamic nucleus, and the septum-diagonal band complex were labeled less frequently. In only one experiment, retrogradely labeled neurons were observed in the ventrolateral hypothalamus and in the brainstem nucleus raphe dorsalis. Since projections from claustrum to the entorhinal cortex has not been studied in the rat with modern sensitive anterograde tracing techniques, iontophoretic injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin were placed into the ventral portion of the claustrum. Anterogradely labeled fibers in the entorhinal area proved not to be confined to the MEA, since a prominent projection distributed to the lateral entorhinal area as well. In both areas, the densest terminal labeling was present in layers IV–VI, whereas layer III appeared to be only sparsely labeled. The present data indicate that of all potential afferents only those from the presubiculum distribute preferentially to layer III of the MEA. This, in turn, suggests a potentially important role of the presubiculum in the seizure-related degeneration of neurons in layer III of the MEA.
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  • 113
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 109 (1996), S. 197-208 
    ISSN: 1432-1106
    Keywords: Superior colliculus ; Pain ; Tectoreticular ; Predorsal bundle ; Approach ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A wealth of evidence implicates the crossed descending projection from the superior colliculus (SC) in orientation and approach behaviours directed towards novel, non-noxious stimuli. In our preceding paper, we identified a population of nociceptive neurones in the rat SC that have axons that project to the contralateral brainstem via this output pathway. The purpose of the present study was, therefore, to evaluate the prediction that the crossed descending projection of the SC is also involved in the control of orientation and approach movements of the head and mouth made during the localisation of persistent noxious stimuli. An independent-groups design was used to test the effects of interrupting the contralateral descending projection from the SC on the behavioural reactions elicited by noxious mechanical stimuli presented to the tail and hindpaws. In different groups of animals, a microwire knife was used to cut the contralateral descending fibres at two different locations: (1) a sagittal cut at the level of the dorsal tegmental decussation; (2) a bilateral coronal cut of the predorsal bundle at the level of the medial pontine reticular formation. Retrograde anatomical tracing techniques were then used to evaluate the effectiveness of the cuts and to assess possible involvement of non-collicular fibre systems in both lesioned and control animals. Additional behavioural procedures were performed to test for general neurological status and responsiveness of animals to non-noxious stimuli. Anatomical tracing data indicated that the largest population of neurones with fibres severed by both cuts were the cells-of-origin of the contralateral descending projection in the intermediate white layer of the SC. Behavioural results showed that significantly more animals in both lesion groups failed to locate and bite a mechanical clip placed on the tail. Instead of switching to motor behaviours to localise and remove noxious stimuli, they persisted with defensive reactions, which included freezing, vocalisation or forward and backward escape. In contrast, when the clip was placed on the hindpaws, it was successfully localised by most lesioned and control animals; however, lesioned animals had reliably longer latencies and spent less time in close contact with the clip. Consistent with the established role of the contralateral descending projection in non-noxious orientation, lesioned animals also showed orienting deficits to a range of non-noxious sensory stimuli. These data suggest that, under certain behavioural circumstances, nociceptive information from the SC is integral to the elaboration of orienting and approach movements of the head and mouth elicited by persistent noxious stimuli.
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  • 114
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 109 (1996), S. 393-398 
    ISSN: 1432-1106
    Keywords: Fictive locomotion ; Mesencephalic locomotor region ; l-Dopa ; 5-Hydroxy-dl-tryptophan ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In adult immobilised, decerebrate rats, administration of l-3,4-dihydroxyphenylalanine, stimulation of the mesencephalic locomotor centre, or a combination of the two elicited fictive locomotor patterns in hindlimb muscle nerves. The patterns correspond closely to those observed in decerebrate animals that were free to move.
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  • 115
    ISSN: 1432-1106
    Keywords: Hippocampal theta rhythm ; Septum ; AP5 ; NMDA ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Theta (θ) rhythm may be mediated, at least in part, by a glutamate neurotransmitter. Thus, in the present study, it was hypothesized that the septum glutamatergic NMDA receptor subtype may be involved in the modulation of physostigmine-induced θ rhythm. To test this hypothesis, we analyzed, in the urethane-anesthetized rat, the effects of septum application of NMDA and d-2-amino-5-phosphonopentanoic acid (AP5), selective and competitive NMDA agonist and antagonist, respectively, on the spectral characteristics of hippocampal θ rhythm elicited by intravenous injection of a anticholinesterase agent, physostigmine. A low dose (16 nmol) of AP5 did not significantly affect EEG recordings, whereas a high dose (50.75 nmol) resulted in significant decreases in phase (-61.8%) at θ frequency, peak θ power (-64.2%), and absolute power of the low-frequency θ band (-67%). These electroencephalographic alterations, which appeared at 50.75 nmol AP5, were amplified following application of massive doses of the drug (121.8 nmol, n=1, and 162 nmol, n=1). Amplification, however, was slight and the θ waves remained clearly detectable. On the other hand, the infusion of NMDA resulted in a significant increase in frequency (+25%) of this rhythm, but this effect was completely antagonized by prior local administration of 16 nmol AP5. Our data suggest that the septal NMDA receptors exert subtle modulatory influences on the septohippocampal cells involved in physostigmine-induced θ wave production, which has not been reported elsewhere: tonic with respect to both low-frequency θ band power and θ phase, and phasic with respect to θ frequency. Our data also indicate that the septum may be a sensitive action site for exogenously administered glutamatergic drugs.
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  • 116
    ISSN: 1432-1106
    Keywords: Malnutrition ; Hippocampus ; Dendrites ; Degeneration ; Regrowth ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have recently shown that lengthy periods of low-protein feeding of the adult rat lead to deficits in the number of hippocampal granule and pyramidal cells, and in the number of mossy fiber synapses. These findings prompted us to analyze the dendrites of these neurons to evaluate whether, under the same experimental conditions, degenerative and/or plastic changes also take place at the dendritic level. The hippocampal formations from five 8-month-old rats fed a low-protein diet (casein 8%) for 6 months from the age of 2 months and from five age-matched controls were Golgi-impregnated and the morphology of the dendritic trees quantitatively studied. We found that in malnourished animals there was a reduction in the number of dendritic branches in the dentate granule cells and in the apical dendritic arborizations of CA3 pyramidal neurons. In addition, in the dentate granule cells the spine density was markedly increased and the terminal dendritic segments were elongated in malnourished animals. No alterations were found in the apical dendrites of CA1 pyramidal cells. The results obtained show that long periods of malnutrition induce marked, although not uniform, changes in the dendritic domain of the hippocampal neurons, which reflect the presence of both degenerating and regrowing mechanisms. These alterations are likely to affect the connectivity pattern of the hippocampal formation and, hence, the activity of the neuronal circuitries in which this region of the brain is involved.
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  • 117
    ISSN: 1432-1106
    Keywords: Transplantation immunology ; Spinal cord ; Cortex ; Ramified and reactive microglia ; Intraocular ; transplantation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract While the central nervous system (CNS) has been characterized as an immunologically privileged site, there are also several reports describing immunological reactions within the CNS. A certain degree of immunological privilege has also been ascribed to the anterior chamber of the eye. We have used the intraocular transplantation model to study immunological reactions in transplants of embryonic neural tissue. Outbred SpragueDawley rats and inbred Fisher rats were used. Pieces of rat parietal cortex or the cervical spinal cord were prepared from embryonic day 14 and implanted into the eye chambers of adult rats of the same strain. Following intraocular maturation, grafts were analysed using antibodies against: major histocompatibility complex (MHC) class I, MHC class II; rat antigens CD4, CD8, CD11b; T-cell receptor; rat antigen ED1; and glial fibrillary acidic protein. Using this set of markers for immunological reactions, transplants were scored on a blind basis. We found no significant differences in immunological scores between transplants obtained from different litters of fetuses of the outbred animals. Grafting in the outbred strain led to increased numbers of immunologically reactive cells in the grafts. This was not seen in grafts in the inbred strain. Spinal cord transplants led to a significantly higher degree of cytotoxic immunity-related cells expressing MHC class II as well as CD4-positive cells. There was a positive correlation between ED1 negativity and well-developed ramified microglia. From these results we conclude also that well-developed intraocular CNS tissue grafts do contain cellular evidence of immunological events and that different areas of the CNS may provoke different degrees of response. Reactive microglial proliferation appears to be one of the most sensitive ways to monitor the immunological condition of grafted CNS tissue.
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  • 118
    ISSN: 1432-1106
    Keywords: Glutamate receptor ; Cerebral cortex ; White matter ; Electron microscopy ; Development ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The distribution of the [3H]alpha-amino-3-hydroxy-5-methylisoxzalepropionic acid (AMPA) receptor subunit GluR4 was studied in frontal, parietal and temporal cerebral cortex, subcortical white matter and corpus callosum of neonatal, immature and mature rats. In 1-to 2-day-old rats, a few oligodendrocyte progenitors and amoeboid microglia in the supraventricular part of the corpus callosum were immunolabelled for GluR4. At 7 to 10 days, the number of amoeboid microglia and oligodendrocyte progenitors in white matter increased; many neurons in cortex, including pyramidal neurons, were also moderately labelled for GluR4. The pattern of GluR4 immunostaining in 14-day-old rats was different from that in 7-to 10-day-old rats, but similar to the adult, in that there was no immunoreactivity in microglia and oligodendrocyte progenitors in subcortical white matter. A proportion of non-pyramidal neurons in cortex were moderately labelled, while some pyramidal neurons were lightly labelled. A population of small glial cells with features of oligodendrocyte progenitors were densely labelled in cortex.
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  • 119
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    Experimental brain research 111 (1996), S. 30-34 
    ISSN: 1432-1106
    Keywords: Dorsal root ganglion cells ; Capsaicin ; Cell diameter ; IH ; Action potential ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of capsaicin were tested on 221 acutely isolated dorsal root ganglion neurons of the rat, which ranged in diameter from 15 to 55 μm. In a subpopulation of these cells, ranging in diameter from 17.5 to 33 μm (n=117), capsaicin (1 μM) produced an inward shift in holding current that was associated with an increase in membrane conductance in most cells (114 of 117). These effects of capsaicin were reversible upon washout of the drug. Other cells ranging in diameter from 15 to 52.5 μm (n=104) were unaffected in this manner by the 1 μm concentration of capsaicin. Capsaicin-sensitive cells had, on average, significantly longer duration action potentials and expressed significantly less IH than capsaicin-insensitive cells. The relatively long duration action potentials and/or small cell body diameter and paucity of IH observed in most of the capsaicin-sensitive cells is consistent with their representing C- or Aδ-type sensory neurons.
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  • 120
    ISSN: 1432-1106
    Keywords: Buccal stretch receptor ; Development ; Static sensitivity ; Masticatory muscles ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Postnatal functional and structural development of the buccal stretch receptor (BSR) of rats was investigated, using electrophysiological and morphological techniques. For functional analysis, sustained discharges in response to ramp-and-hold stretches were recorded from the BSRs isolated from animals aged 10 days to 10 weeks. The threshold amplitude of stretch for a sustained discharge fell significantly between 10 days and 3 weeks, reaching adult values at 5 weeks of age, while the static sensitivity increased conspicuously between 2 and 4 weeks after birth. On the other hand, between 1 and 4 weeks of age, apparent structural changes in the BSR were observed on the number of preterminal branches in a sensory unit, the size of the varicose-like swellings along the terminal axon, the density of collagen and elastic fibers around the core structure, and the content of the sub-capsular space. From these results, we suggest that the increase in the density of the connective tissue around the core structure is associated with an enhancement in the elasticity of the BSR in the early postnatal stages, decreasing the threshold amplitude of stretch for a sustained discharge. One possible explanation for the maturation of the static sensitivity of this receptor is growth of the sensory axon terminals filled with dense mitochondria.
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  • 121
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    Experimental brain research 111 (1996), S. 371-384 
    ISSN: 1432-1106
    Keywords: Purkinje cell ; Estradiol ; Network ; Performance ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Neuromodulation of Purkinje (Pnj) cell responses by monoamines and estrous hormones is well characterized in the cerebellum at the cellular level, but not at the level of neuronal circuits in the awake behaving animal. In the present study, simultaneous recordings of up to 16 single neurons from within the olivo-cerebellar circuit were obtained through chronically implanted microwire electrode bundles: arrays of Pnj cell like neurons (Pnj cln) in the paravermal cerebellum and neurons within the afferent source of its climbing fiber input, the rostral dorsal accessory olive (rDAO), were recorded simultaneously across 3–20 consecutive estrous cycles during constant or variable speed treadmill locomotion performance tasks. Over 90% of Pnj cln recorded during treadmill locomotion exhibited significant increases (80%) or decreases (10%) in activity correlated with the stance phase of locomotion. In contrast, cells from the rDAO increased activity during speed changes or when the rat failed to maintain the treadmill speed (position slip). On the night of behavioral estrus, which is triggered by elevations in circulating levels of 17β-estradiol and progesterone, the magnitude of both increases and decreases in stance-correlated Pnj cln activity increased by 85–115%. These results are consistent with our previous findings that 17β-estradiol and progesterone enhance excitatory and inhibitory responses of single Pnj cells to locally applied glutamate and GABA, respectively. This dual enhancement of both excitatory and inhibitory effects, apparently paradoxical at the cellular level, produced a marked heightening of the contrast of the neural population “signal” at the neuronal ensemble level. Furthermore, the stance-correlated discharge of Pnj cln during estrus preceded that during diestrus by ∼120ms. Frame-by-frame video analysis also suggested that the swing phase of the step cycle was shortened on estrus compared with diestrus (low hormone state). In addition, rDAO discharge correlated with speed change or position slip was also significantly increased (P〈0.05) on the night of behavioral estrus versus diestrus. Thus, estrus was associated with changes in both the amplitude and the timing of Pnj cln and rDAO discharge correlated with specific behavioral events. These estrous-associated changes in Pnj cell activity were well correlated (r = 0.84) with faster responses to random changes in treadmill speed, a motor performance task. Together, these findings suggest that the increases in the contrast of stancecorrelated Phj cln discharge observed following peak circulating levels of sex steroid hormones are associated with improved motor performance on a randomly moving treadmill.
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  • 122
    ISSN: 1432-1106
    Keywords: Tachykinin receptor ; Retrograde cell labeling ; Optic nerve crush ; Ganglion cell layer ; Inner nuclear layer ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Substance P receptor is known to provide a principal interface between tachykinin peptides and tachykinin-sensitive cells in retinal circuitry and to produce several physiological functions such as excitation of ganglion cells. We reported results of in situ hybridization analysis of substance P receptor in rat retina using digoxigenin-labeled RNA probes to yield discrete cell labeling. Distinct hybridization signal was present in a great majority of ganglion cells that provide retinal fibers to a central target. It was also present in a subpopulation of amacrine cells. Following optic nerve crush, ganglion cells lost their hybridization signal in a time-dependent manner, while hybridization-positive amacrine cells were persistently seen. From the results, we identified the hybridization message as distinctly localized to two systems, output cells and intrinsic cells in retinal circuitry.
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  • 123
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    Experimental brain research 110 (1996), S. 21-27 
    ISSN: 1432-1106
    Keywords: Long-term potentiation ; Auditory cortex ; Pyramidal cell ; NMDA receptor ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In supragranular layers of the rat auditory cortex, white matter stimulation produces antidromic and transsynaptic field potentials, of which only the latter shows long-term potentiation (LTP) following tetanic stimulation of the white matter. In this study, we investigated the cells responsible for the LTP. The transsynaptic field potentials, excitatory postsynaptic potentials (EPSPs), and orthodromic spikes were blocked by 6-cyano-7-nitroquinoxaline-2, 3-dione (10 μM), but not by d-2-amino-5-phosphonovalerate (D-AP5, 50 μM). The latency of EPSPs was constant, while that of transsynaptic field potentials and orthodromic spikes was shortened by the increase in stimulus intensity. Appearance of anti-dromic field potentials and antidromic spikes at strong stimulus intensities were accompanied by reduction in amplitude of transsynaptic field potentials and elimination of orthodromic spikes, respectively. Morphological identification of neurons showing antidromic spikes by intracellular injection of biocytin revealed that most of them were supragranular pyramidal cells. The effects of tetanic stimulation were studied by intracellular recording in seven neurons showing, antidromic spikes, and it was found that only two of them showed LTP of EPSP slope. However, in all of the other eight units showing antidromic spikes and recorded extracellularly, LTP was clearly observed in orthodromic firing probability. The LTP induction in the orthodromic firing probability was blocked by D-AP5. These findings indicate that the LTP in field potentials corresponds to LTP in supragranular pyramidal outputs, and the input-output relationship in neural networks of the adult rat auditory cortex is strongly modulated by LTP.
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  • 124
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    Experimental brain research 112 (1996), S. 431-441 
    ISSN: 1432-1106
    Keywords: Plasticity ; Auditory cortex ; Neuronal assemblies ; Microstimulation ; Cortical maps ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Single neurons, acting alone, cannot account for the complex and rapid computations that are routinely accomplished by the behaving nervous system. Recent studies with separable multineuron recordings are showing that neuronal assemblies can indeed be detected and that their organization is very dynamic, depending on variables such as time, physical stimulus, and context. Here we explore both single-neuron and assembly properties in the rat's auditory cortex. Acoustic stimuli are used as a normal, physiological input, and weak electrical intracortical microstimulation (ICMS) as a perturbation that forces a rapid cortical reorganization. In this setting, various aspects of neuronal interactions are changed by the ICMS. We found that cortical neurons exhibited highly synchronous oscillatory firing patterns that were enhanced by ICMS. Cross-correlation studies between two spike trains showed that statistically significant correlations depended on the anatomical distance between the two neurons. ICMS changed the strength and the local number of such correlations. Joint petristimulus analysis and gravity analysis showed that the correlation between neuronal activities varied dynamically at several time scales. We have identified neuronal assemblies in two ways, defined through similarity of receptive field properties and defined through correlated firing. Close anatomical spacing between neurons was conducive to, but not sufficient for membership in, the same assembly with either definition. ICMS changed cortical organization by altering assembly membership. Our data show that neuronal assemblies in the rat auditory cortex can be established transiently in time and that their membership is dynamic.
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  • 125
    ISSN: 1432-1106
    Keywords: Infraorbital nerve ; Barrels ; Trigeminal ; Immunocytochemistry ; Peptides ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous studies in adult animals have suggested that the peptides galanin and neuropeptide Y (NPY) may be upregulated in the same primary afferent neurons after peripheral axotomy. The present study was undertaken to determine whether such upregulation occurred in vibrissae-related primary afferent neurons and their axons after damage to the infraorbital nerve [ION; the trigeminal (V) branch that innervates the vibrissae follicles]. Double-labelling experiments demonstrated that approximately 75% of axotomized V ganglion cells and the central arbors of vibrissae-related primary afferents expressed both galanin and NPY after perinatal, but not adult, nerve damage. However, additional experiments demonstrated that the sensitive periods for lesion-induced upregulation of the two peptides and the period over which they were expressed after neonatal ION transection differed substantially. Staining for both peptides was increased after ION damage on P-0 through P-14, but only galanin staining was increased in vibrissae-related primary afferents after lesions on P-21. Galanin expression was elevated in vibrissae-related primary afferents in rats killed 3,8, and 15 days after neonatal ION transection, while increased NPY was observed at only the middle time point. The lesion-induced increases in galanin and NPY in vibrissae-related ION primary afferents suggest that these peptides may modulate central V reorganization after such damage.
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  • 126
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    European journal of pediatrics 155 (1996), S. 561-567 
    ISSN: 1432-1076
    Keywords: Key words Glycogen deficiency ; Glycogen synthase ; Ketotic ; hypoglycaemia ; Corn (maize) ; starch ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Three children from two German families are described and the observations compared with the previously published three families comprising eight patients. The two index cases presented with morning fatigue, had ketotic hypoglycaemia when fasting which rapidly disappeared after eating, and hepatic glycogen deficiency and absent or very low hepatic glycogen synthase activity. Metabolic profiles comprising glucose, lactate, alanine, and ketones in blood were typical for hepatic glycogen synthase deficiency. Symptoms were rapidly relieved and chemical signs corrected by introducing frequent protein-rich meals and night-time feedings of suspensions of uncooked corn (maize) starch. The discovery of oligosymptomatic and asymptomatic siblings suggests that there are more persons with undiagnosed hepatic glycogen synthase deficiency. Conclusion Liver glycogen synthase deficiency is likely to be more common than is believed today. It should be sought in children who, before the first meal of the day, present with drowsiness, lack of attention, pallor, uncoordinated eye movements, disorientation or convulsions and who have hypoglycaemia and acetone in urine.
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  • 127
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    European journal of pediatrics 155 (1996), S. 561-567 
    ISSN: 1432-1076
    Keywords: Glycogen deficiency ; Glycogen synthase ; Ketotic hypoglycaemia ; Corn (maize) starch ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Three children from two German families are described and the observations compared with the previously published three families comprising eight patients. The two index cases presented with morning fatigue, had ketotic hypoglycaemia when fasting which rapidly disappeared after eating, and hepatic glycogen deficiency and absent or very low hepatic glycogen synthase activity. Metabolic profiles comprising glucose, lactate, alanine, and ketones in blood were typical for hepatic glycogen synthase deficiency. Symptoms were rapidly relieved and chemical signs corrected by introducing frequent protein-rich meals and night-time feedings of suspensions of uncooked corn (maize) starch. The discovery of oligosymptomatic and asymptomatic siblings suggests that there are more persons with undiagnosed hepatic glycogen synthase deficiency.
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  • 128
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    Experimental brain research 108 (1996), S. 285-296 
    ISSN: 1432-1106
    Keywords: Acetylcholine ; Amygdala ; Basal forebrain ; Electrocorticogram ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In urethane-anesthetized rats, electrical 100-Hz stimulation of the basal amygdala changed neocortical electrical activity from 6-Hz or less large-amplitude, irregular slow activity to low-voltage fast activity (LVFA) including frequencies of above 10 Hz. A similar activating effect was seen in the hippocampus, where amygdala stimulation induced the appearance of rhythmical slow activity in the 2 to 6-Hz range. This activation of neocortical and hippocampal activity by amygdala stimulation was blocked by the cholinergic-muscarinic receptor antagonist scopolamine (0.5–5.0 mg/kg i.p.), but not by the peripheral antagonist methylscopolamine, in a concentration-dependent manner. In contrast, a blockade of ascending inputs from the midbrain to the neocortex by treatment with the serotonin-depletor p-chlorophenylalanine or cauterization of the rostral midbrain did not block neocortical LVFA to amygdala stimulation, even though the lesions abolished all LVFA to strong noxious stimuli such as tail pinches. Unilateral infusions of the local anesthetic lidocaine (1%) into the basal forebrain selectively blocked LVFA in the neocortex ipsilateral to the infusion. However, intracerebral or systemic administration of various excitatory amino acid antagonists (2-amino-5-phosphonovaleric acid, kynurenic acid, NPC 12626) was not effective in blocking LVFA to amygdala stimulation. An input from the amygdala to the basal forebrain cholinergic system appears to be one of multiple systems involved in the cholinergic activation of neocortical and hippocampal activity. Further, basal forebrain-cholinergic inputs to the cerebrum alone are sufficient to activate the electrocorticogram, as they sustain activation even in the absence of inputs from the mesencephalon.
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  • 129
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    Experimental brain research 109 (1996), S. 17-21 
    ISSN: 1432-1106
    Keywords: Circling ; Habenula ; Apomorphine ; Haloperidol ; Dopamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Apomorphine, 2 mg/kg (s.c.) produced significant contralateral turning in rats with unilateral radiofrequency lesions of the habenula nucleus over a test period of 60 min when tested at post-surgery days 3, 7, and 14. Levels of contralateral circling were not significantly increased when the animals were tested on days 21 and 28, although a contralateral bias was still observed. Rotation induced by apomorphine was completely blocked by the administration of haloperidol (0.3 mg/kg i.p.), and there was no behavioural asymmetry in lesioned animals following administration of saline or a high dose of haloperidol (2 mg/kg i.p.). These results indicate that unilateral habenula lesions lead to imbalance of dopaminergic activity, which is expressed as contralateral circling when the animal is challenged with apomorphine.
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  • 130
    ISSN: 1432-1106
    Keywords: Sensory neurons ; Proto-oncogenes ; Corneal pain ; Calcium channel blockers ; Diltiazem ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The distribution and number of trigeminal brainstem and higher order sensory neurons expressing the protein product of the proto-oncogene c-fos after noxious stimulation of the cornea was studied in the rat using immunocytochemistry. The possibility that attenuation of nociceptive messages from the cornea by diltiazem reduced Fos-like immunoreactivity of spinal trigeminal neurons was also examined. A group of animals were killed 2–3 h after corneal stimulation. One cornea was stimulated with: a drop of 10 mM acetic acid; with acid plus mechanical scratching of the corneal epithelium; or with a drop of saline at 56 ° C. Half of the animals treated with acid had been pretreated ipsilaterally with topical diltiazem (10 mM). Control rats received either saline in one eye or no treatment. Another group of animals were killed 7–8 h after stimulation with acetic acid. Fos-like immunoreactive neurons were counted in serial brain-stem sections using an anti-Fos primary antiserum and processed according to the avidin-biotin complex method. In rats killed 2–3 h after corneal stimulation with acid, heat, or acid plus mechanical injury, labelled neurons were found in laminae I and II of the intermediate zone between caudalis and interpolaris subnuclei of the ipsilateral spinal trigeminal nucleus and, in a reduced number, in the symmetrical zones of the contralateral side. In animals stimulated with noxious heat or combined mechanical and chemical injury, a few scattered cells were also labelled in the ipsilateral junction between the cervical spinal cord and the caudalmost part of the trigeminal subnucleus caudalis. In rats killed 7 h after stimulation with acid, stained neurons were observed in the same areas of the trigeminal nucleus as in rats killed at shorter times, but in lower numbers; in these animals, no immunoreactive cells were found in deeper laminae or in higher sensory relay nuclei. Pretreatment with diltiazem significantly reduced the number of cells of the spinal trigeminal nucleus labelled after corneal stimulation with acid. The results indicate that brief noxious stimulation of the cornea evoke expression of c-Fos in neurons of the spinal trigeminal complex. Diminution by diltiazem of the number of immunreactive neurons activated by corneal irritation suggests that this drag, by reducing chemosensitivity of nociceptive terminals, decreases nociceptive inflow to central nervous structures involved in ocular pain perception.
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  • 131
    ISSN: 1432-1106
    Keywords: Urinary bladder ; Inflammation ; Brainstem ; Pontomesencephalic junction ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The evoked expression of the immediate early gene encoded proteins c-Fos and Krox-24 was used to study activation of hindbrain neurons as a function of the development of Cyclophosphamide (CP) cystitis in behaving rats. CP-injected animals received a single dose of 100 mg/kg i.p. under transient volatile anesthesia and survived for 1 to 4 h in order to cover the whole postinjection period during which the disease develops. CP-injected groups included: (1) animals with minor simple chorionic edema, an early characteristic of inflammation (1 h postinjection); (2) animals with well developed simple chorionic edema (2 h postinjection); (3) animals with mild inflammation (chorionic edema accompanied by epithelial cleavage; 3 h postinjection); and (4) animals with complete inflammation (4 h postinjection). In addition to onset of chorionic edema, the earliest postinjection period also included the general aspects of the nervous reaction consecutive to the injection process (handling, transient volatile anesthesia and postanesthesia awakening, abdominal pinprick, CP blood circulating effects). Controls included both noninjected animals and saline injected animals surviving for the same times as CP injected ones. Quantitative results come from c-Fos expression. It has been shown that: (1) saline injection is a significant stimulus for only nucleus O and central gray pars alpha and nucleus medialis of the dorsal vagal complex; (2) all structures driven by CP injection (nucleus O and central gray pars alpha, locus coeruleus, Barrington's nucleus and parabrachial area mostly in its ventral and lateral subdivisions, dorsal vagal complex, ventrocaudal portion of lateral bulbar reticular formation) responded vigorously shortly after injection, but only two (dorsal vagal complex, ventrocaudal portion of lateral bulbar reticular formation) showed increased or renewed activity when cystitis completely developed, i.e., when noxious visceral inputs reached highest levels. Regarding the sequential activation of these structures in relation to postinjection time, evidence is given that: (1) a large variety of hindbrain structures are differentially involved in either the general reaction consecutive to the injection process or to various degrees of cystitis; (2) these structures extend from the brain spinal cord to the pons mesencephalon transitional junction levels; (3) the two structures most powerfully driven by visceronociceptive inputs are also the most caudal ones, being located at the brain spinal cord junction level; and (4) the dorsal vagal complex could be the main hindbrain visceral pain center, with three particular subdivisions, the nucleus medialis, nucleus commissuralis, and ventralmost part of area postrema, being involved.
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  • 132
    ISSN: 1432-1106
    Keywords: Calcium ; Hippocampal slice ; CA1 ; ω-Agatoxin IVA ; ω-Conotoxin GVIA ; ω-Conotoxin ; MVIIC ; Nimodipine ; Ethosuximide ; Trimethadion ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The contribution of T-, L-, N-, P-, and Q-type Ca2+ channels to pre-and postsynaptic Ca2+ entry during stimulus-induced high neuronal activity in area CA1 of rat hippocampal slices was investigated by measuring the effect of specific blockers on stimulus-induced decreases in extracellular Ca2+ concentration ([Ca2+]0). [Ca2+]0 was measured with ion-selective electrodes in stratum radiatum (SR) and stratum pyramidale (SP), while Ca2+ entry into neurons was induced with stimulus trains (20 Hz for 10 s) alternately delivered to SR and the alveus, respectively. The [Ca2+]0 decreases recorded in SR in response to SR stimulation represented mainly presynaptic Ca2+ entry (Capre), while [Ca2+]0 decreases recorded in SP in response to alvear stimulation were predominantly based on postsynaptic Ca2+ entry (Capost). Ethosuximide and trimethadione were ineffective m concentrations up to 1 mM. At 10 mM, they reduced Capost and, much less, also Capre Nimodipine (25 μM) reduced Capost and, to a minor extent, Capre. ω-Agatoxin IVA (0.4–1 μM) and ω-conotoxin MVIIC (1 μM) also reduced both Capre and Capost, but with a stronger action on Capre. ω-Conotoxin GVIA (3–8 μM) reduced Capost without effect on Capre. We conclude that during stimulus-induced, high-frequency neuronal activity Capost is carried by P/Q-, N-, and L-type channels and probably a further channel type different from these channels. Capre includes at least P/Q-and possibly L-type channels. N-type channels did not contribute to Capre in our experiments. Since ethosuximide and trimethadione were only effective in high concentrations, their action may be unspecific. Thus, T-type channels do not seem to play a major part in Ca2+ entry in this situation.
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  • 133
    ISSN: 1432-1106
    Keywords: Cerebral ischemia ; Magnetic resonance imaging ; Hyperglycemia ; Diffusion imaging ; Reperfusion ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The early evolution of ischemic brain injury under normoglycemic and streptozotocin-induced hyperglycemic plasma conditions was studied using magnetic resonance imaging (MRI). Male Sprague-Dawley rats were subjected to either permanent middle cerebral artery occlusion (MCAO), or 1-h MCAO followed by reperfusion using the intraluminal suture insertion method. The animals were divided into four groups each with eight rats: normoglycemia with permanent MCAO, normoglycemia with 1-h MCAO, hyperglycemia with permanent MCAO, and hyperglycemia with 1-h MCAO. Diffusion-weighted images (DWIs) and T2-weighted images (T2WIs) were aquired every l h from 20 min until 6 h after MCAO, at which time cerebral plasma volume images (PVIs) were acquired. Tissue infarction was determined by triphenyltetrazolium chloride staining at 7 h after MCAO. The ischemic damage, measured as the area of DWI and T2WI hyperintensity and tissue infarction, increased significantly in hyperglycemic rats in both permanent and transient MCAO models. In the permanent MCAO model, the maximal apparent water diffusion coefficient (ADC) decline under either normoor hyperglycemia was about 40%, but the speed of ADC drop was faster in hyperlgycemic rats than in normoglycemic rats. Reperfusion after l h of MCAO in normoglycemic rats partly reversed the decline in ADC, whereas the low ADC area continued to expand after reperfusion in the hyperlgycemic group. Between the two hyperglycemic groups with either permanent MCAO or reperfusion, no significant difference was found in the infarct volume measured at 7 h after MCAO. However, reperfusion dramatically increased the extent and accelerated the development rate of vasogenic edema. ADC in the hyperglycemic reperfusion group also dropped to a lower level. A large “no-reflow” zone was found in the ischemic hemisphere in the hyperglycemic reperfusion group. This study provides strong evidence to support that preischemic hyperglycemia exacerbates ischemic damage in both transient and permanent MCAO models and demonstrates, using MRI, that reperfusion under preischemic hyperglycemia accelerates the evolution of early ischemic injury.
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  • 134
    ISSN: 1432-1106
    Keywords: Differential-pulse voltammetry ; Dopamine ; Caudate putamen ; Neural grafting ; Non-grafted side ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study employed differential-pulse voltammetry to assess the influence of foetal ventral mesencephalic grafts on dopamine overflow in the contralateral caudate putamen of the 6-hydroxydopamine rat model of Parkinson's disease. The experimental design involved measurements of dopamine overflow in the grafted and contralateral striatum. Control measurements of dopamine overflow were performed in 6-hydroxydopamine-lesioned rats only and the caudate putamen of normal control rats. Cell suspensions of foetal rat ventral mesencephalic tissue were grafted into the dopamine-depleted caudate putamen of unilaterally 6-hydroxydopamine-lesioned rats. At 6 weeks, animals with functional, mature grafts (as assessed by amphetamine-amplified behavioural asymmetry), were pretreated with pargyline (75 mg/kg i.p.), and both striatal sides were monitored for dopamine overflow for 90 min following amphetamine sulphate administration (5 mg/kg i.p.). The time course of dopamine overflow inside the graft was similar to that in the contralateral caudate putamen of the same animal, the normal control animal and the contralateral caudate putamen of 6-hydroxydopamine-lesioned animals. However, in grafted animals the mean dopamine overflow detected in the contralateral caudate putamen was approximately 34% lower than the concentration of dopamine detected in the contralateral caudate putamen of 6-hydroxydopamine-lesioned control animals and approximately 39% lower than the concentration of dopamine detected in the caudate putamen of the normal control animal. There was no statistical difference in the concentration of amphetamine-induced dopamine overflow between the caudate putamen contralateral to the 6-hydroxydopamine lesion and the caudate putamen of the normal control animal. These data suggest that intrastriatal foetal ventral mesencephalic suspension grafts reduce amphetamine-induced dopamine release in the contralateral non-grafted caudate putamen.
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  • 135
    ISSN: 1432-1106
    Keywords: Trigeminal nerve ; Primary afferents ; Synapses ; Ultrastructure ; Vibrissae ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Neonatal transection of the infraorbital nerve (ION; the trigeminal, V, branch that supplies the mystacial vibrissae follicles) results in an upregulation of galanin in the central arbors of primary afferent axons. The present study was undertaken to evaluate the synaptic organization of these galanin-positive primary afferents and compare it with that of normal neurobiotin/biocytin-labeled primary afferent axons from animals of the same age. Examination of 1200 neurobiotin/biocytin-labeled profiles in V nucleus principalis (PrV) of rats killed on postnatal day (P-) 7 indicated that 23.3% (n=279) of these profiles made synaptic contacts: 87.4% were axodendritic, 8.9% were axoaxonic, 2.8% were axosomatic, and 0.7% were axospinous. Evaluation of 1200 galanin-positive profiles in PrV from rats that sustained transection of the ION on P-0 and were killed on P-7 indicated that only 64 (5.3%) of these profiles made synaptic contacts (P〈0.05 compared with the intact animals). Of the galanin-positive profiles that did make synapses in PrV, 81.2% (n=52) were axodendritic and 18.8% (n=12) were axoaxonic. These results indicate that galanin released by damaged ION primary afferents in PrV is likely to affect the activity of second-order V neurons by a paracrine action rather than by acting at specific synapses.
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  • 136
    ISSN: 1432-1106
    Keywords: Calcium current ; Cerebellar granule neuron ; Heloderma ; Helodermine ; Ion channel block ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Helothermine (HLTx), a 25.5-kDa peptide toxin isolated from the venom of the Mexican beaded lizard (Heloderma horridum horridum), was found to be an inhibitor of Ca2+ channels in cerebellar granule cells of newborn rats. Macroscopic currents, carried by 10 mM Ba2+, were measured in whole-cell configuration. The toxin at the saturating dose of 2.5 μM reversibly produced an ≈67% block of the voltage-dependent Ca2+ current by a fast mechanism of action. The current inhibition and recovery were reached in less than 1 min. Inhibition was concentration-dependent, with a half-effective dose of 0.25 μM. The current block was practically voltage-independent, whereas the steady-state inactivation h ∞ was significantly affected by HLTx (≈10 mV). The toxin did not affect the activation and inactivation kinetics of the Ca2+ current. Experiments with other Ca2+ channel blockers showed that HLTx abolished ω-conotoxin GVIA-sensitive Ca2+ currents, as well as ω-AgaIVA- and dihydropyridine-sensitive Ca2+ currents. These drugs had virtually no effect when HLTx was applied first. The present results indicate that HLTx produce a high-potency blockage of the three pharmacologically distinct Ca2+ current components.
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  • 137
    ISSN: 1432-1106
    Keywords: Intracortical microstimulation ; c-fos ; Ca2+/calmodulin-dependent protein kinase II ; Glutamic acid decarboxylase ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Long-train tetanic stimulation of the cerebral cortex induces long-term changes in the excitability of cortical neurons, while short-train electrical stimulation does not. In the present study, we show that both forms of stimulation when applied to rat motor cortex for 4 h enhance c-fos expression, but only tetanic stimulation, when imposed upon short-train stimulation, modulates gene expression for 67-kDa glutamic acid decarboxylase (GAD) and alpha Ca2+/calmodulin-dependent protein kinase II (CaMKIIα). Gene expression for beta Ca2+/calmodulin-dependent protein kinase II is not affected by either stimulation mode. GAD messenger RNA (mRNA) is increased from 1 h after the end of tetanization to the longest poststimulus survival time investigated (14 h). CaMKIIα mRNA is decreased 1–3 h after the end of tetanization but thereafter returns to prestimulus levels. These results imply not only that mechanisms underlying neocortical plasticity are stimulus-dependent but also that they involve reciprocal changes in molecules regulating the balance of excitation and inhibition.
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  • 138
    ISSN: 1432-1106
    Keywords: Neural transplantation ; Parkinson's disease ; Tissue cultures ; Mesencephalon ; Human embryo ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Free-floating roller tube cultures of human fetal (embryonic age 6–10 weeks post-conception) and rat fetal (embryonic day 13) ventral mesencephalon were prepared. After 7–15 days in vitro, the mesencephalic tissue cultures were transplanted into the striatum of adult rats that had received unilateral injections of 6-hydroxydopamine into the nigrostriatal bundle 3–5 weeks prior to transplantation. Graft survival was assessed in tyrosine hydroxylase (TH)-immunostained serial sections of the grafted brains up to post-transplantation week 4 for the human fetal xenografts and post-transplantation week 11 for the rat fetal allografts. d-amphetamine-induced rotation was monitored up to 10 weeks after transplantation in the allografted animals and compared with that of lesioned-only control animals. All transplanted animals showed large, viable grafts containing TH-immunoreactive (ir) neurons. The density of TH-ir neurons in the human fetal xenografts and in rat fetal allografts was similar. A significant amelioration of the amphetamine-induced rotation was observed in the animals that received cultured tissue allografts. These results promote the feasibility of in vitro maintenance of fetal human and rat nigral tissue prior to transplantation using the free-floating roller tube technique.
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  • 139
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    Experimental brain research 110 (1996), S. 347-359 
    ISSN: 1432-1106
    Keywords: Glutamate ; Aspartate ; Developing neocortex ; Immunocytochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The excitatory amino acids l-glutamate and l-aspartate are believed to be utilized as neurotransmitters by the pyramidal neurons in the mammalian cerebral cortex. These cells can be recognized early in development, while glutamate might play an important part in the maturation and plasticity of the cortex. Here, we used light and electron microscopic immunocytochemistry to study the time of appearance and maturation of glutamate and aspartate in neurons of the rat visual cortex. Glutamate- and aspartate-immunoreactive cells were first detected in deep cortical layers at postnatal day 3. During the next 3 weeks, labelled neurons were observed progressively in more superficial layers, but did not demonstrate their adult pattern of distribution until postnatal week 4. Electron microscopic analysis showed that glutamate- and aspartate-labelled neurons gradually develop their cytological and synaptic features during the first 4 postnatal weeks, with this process of differentiation originating in the deep cortical layers and progressively extending to the superficial layers. These findings suggest that cortical pyramidal neurons begin to express detectable levels of transmitter glutamate and/or aspartate after they have completed their migration. Their neurochemical differentiation follows an “inside-out” pattern similar to the pattern described for the genesis and morphological differentiation of this population of cortical neurons.
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  • 140
    ISSN: 1432-1106
    Keywords: Superior colliculus ; Turning ; Cerebellum ; Substantia nigra ; Basal ganglia ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In a recent electrophysiological experiment, we showed the deep cerebellar nuclei to be a major source of excitatory input to the superior colliculus. Furthermore, target neurons in the colliculus were found, in every case, to receive convergent tonic inhibitory input from the substantia nigra pars reticulata. In the present study, we investigated these effects in the awake rat. We asked whether circling behaviour, induced by unilateral injection of a GABA antagonist into the lateral colliculus, could be suppressed by concurrent cerebellar inactivation. Rats were chronically implanted with bilateral guide cannulae located above the superior colliculus and deep cerebellar nuclei. Bicuculline methiodide (25 pmol) was microinjected unilaterally into intermediate layers of the colliculus at increasing depths until an optimal contralateral circling response was elicited. This behaviour was taken as the “baseline response” and was the first of three treatments. The second was an identical manipulation of the colliculus with a concurrent 200-nl microinjection of 1 M GABA into the contralateral deep cerebellar nuclei. The third was a repeat of BIC alone into the colliculus or, if rotation had been suppressed by more than 50% on test 2, the treatment was collicular BIC plus deep cerebellar saline. This latter treatment was used as a control for possible non-pharmacological injection effects. The effect of cerebellar GABA at 26 sites (17 within cerebellar nuclei and 9 outside) on BIC-induced rotation at 15 collicular sites was studied in ten animals. Only GABA injections at sites that fell within the cerebellar nuclei significantly reduced turning (P〈0.0001). A full behavioural analysis showed that this was a specific suppression of turning, not the result of general motor impairment. These results provide clear behavioural evidence that opposing, convergent influences from the basal ganglia and cerebellum interact in the lateral superior colliculus to control head and body movements. They furthermore suggest that the tonic deep cerebellar excitation of the superior colliculus could be the driving force in the expression of rotation induced by manipulations of the basal ganglia.
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  • 141
    ISSN: 1432-1106
    Keywords: Cell death ; Neurotrophins ; Retrograde labeling ; Tyrosine hydroxylase ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Intraparenchymal injections of the neurotoxin 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle in rats destroys the dopaminergic neurons in the pars compacta of the substantia nigra. In other transmitter systems it has been found that axotomy or neurotoxin exposure produces an initial loss of neurotransmitter phenotype, with cell death occurring over a much slower time course. To determine whether this also occurs in dopamine neurons after 6-OHDA, two approaches were utilized. First, the effect of injections of 6-OHDA into the medial forebrain bundle on nigral dopaminergic neurons was studied using combined fluorogold and immunocytochemical labeling. Four weeks after the 6-OHDA injection, there was an 85% reduction in the number of tyrosine hydroxylase (TH)-immunoreactive cells on the lesioned side. In contrast, there was only a 50% reduction in the number of fluorogold-labeled cells on the lesioned side. Second, the time course of the rescue of dopaminergic neurons after 6-OHDA by glial cell line-derived neurotrophic factor (GDNF) was determined using TH immunocytochemistry. Greater numbers of dopamine neurons were rescued 9 weeks after GDNF, compared with counts made 5 weeks after GDNF. Taken together, these results suggest loss of dopaminergic phenotype is greater than cell loss following 6-OHDA injections, and that GDNF restores the phenotype of affected cells.
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  • 142
    ISSN: 1432-1106
    Keywords: Male sexual behavior ; Vasopressin ; Limbic system ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract During sexual behavior in the male rat, peptidergic cells in the medial amygdaloid nucleus become active and release a vasopressin-like peptide. The present experiments were designed to examine hippocampal changes as a result of this peptide's action during sexual behaviors. Chronic field-potential recordings from the hippocampus of male rats were acquired in a wide variety of social and nonsocial circumstances. Hippocampal responses that resemble the known action of the vasopressin-like peptide were seen only with social stimuli such as sexual stimuli and stimuli that led to aggressive behavior between males. The results show that the occasions of peptide action in the hippocampus correlate with the occasions of peptide release as determined by recording from the peptidergic cell bodies. The results are interpreted to indicate that the amygdala projection to the hippocampus has a special role to play in social behavior.
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  • 143
    ISSN: 1432-1106
    Keywords: Retrorubral field ; Hippocampal formation ; Mesolimbic dopaminergic system ; Phaseolus vulgaris leucoagglutinin ; Tyrosine hydroxylase immunohistochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The dopaminergic neurons in the midbrain of the rat are located in three groups: the ventral tegmental area (VTA-A10), substantia nigra (SN-A9), and retrorubral field (RRF-A8). We have recently examined the organization of the projections from the VTA and the SN to the hippocampal formation (HF) in the rat. In the present study we characterize the projections of the RRF to the HF by using anterograde tracing, retrograde tracers, and tyrosine hydroxylase (TH) immunohistochemistry. Following iontophoretical injections of Phaseolous vulgaris leucoagglutinin (PHA-L) into the RRF, anterograde labeling was observed primarily in the ipsilateral subiculum and adjacent CA1 cell field. Sparse labeling was also observed in the CA3 cell field and dentate gyrus. The distribution of RRF neurons projecting to the HF was examined by injecting retrograde fluorescent tracers (fluorogold, fast blue, and nuclear yellow) into several hippocampal areas. The retrograde tracer findings indicate that the medial aspects of the RRF project to the subiculum and adjacent CA1 cell field of both the septal and temporal HF. In order to evaluate the percentage of dopaminergic cells of the RRF projecting to the HF, the retrograde neuronal tracer fluorogold was used in combination with TH immunohistochemistry. The quantitative evaluation of retrograde labeled and TH-immunoreactive (IR) cells showed that RRF projections to the HF are partially (10–18%) dopaminergic. The findings suggest that the general pattern of distribution and organization of the RRF-A8 projections to the HF is similar to that observed in our previous studies examining hippocampal afferents from the VTA and SN. The data also suggest a crude topographical organization of RRF afferents to the HF and a more prominent input to the temporal than to the septal HF.
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  • 144
    ISSN: 1432-1106
    Keywords: Perinatal asphyxia ; Dopamine utilization ; Tyrosine hydroxylase activity ; Substantia nigra ; Neostriatum ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study was undertaken in order to study the effects of perinatal asphyxia on tyrosine hydroxylase (TH) activity, dopamine levels and turnover, and dopamine metabolites (3,4-dihydroxyphenylacetic acid, DOPAC, homovanillic acid, HVA, and 3-methoxytyramine, 3-MT, analyzed by high-performance liquid chromatography, HPLC) measured in the basal ganglia of the 20- to 40-min-old newborn and 4-week-old male rat. Asphyxia was induced in pups by placing the fetuses, still in their uterus horns removed by hysterectomy from pregnant rats at full term, in a 37°C water bath for 15–16 min or 19–20 min. Following asphyxia, the uterus horns were opened, and the pups were removed and stimulated to breathe. A 100% and 50–80% pup survival was obtained following 15–16 min and 19–20 min of asphyxia, respectively. Acute changes were studied in brains from newborn pups 20–40 min after delivery, and long-term changes were studied in brains from 4-week-old rats. No changes in TH-activity could be observed in the substantia nigra/ventral tegmental area (SN/VTA), the striatum, or the accumbens nucleus/olfactory tubercle (ACC/TUB), in the newborn or the 4-week-old rat. In the newborn rat, 19–20 min of asphyxia increased (as compared to controls) dopamine levels in the SN/VTA to 136±14% and in the ACC/TUB to 160±10%, indicating an increased synthesis and/or release of dopamine. DOPAC levels were increased in the SN/VTA to 150±14% and in the ACC/TUB to 151±10%, and HVA levels were increased to 152±16% in the striatum and to 117±4% in the ACC/TUB. Following 15–16 min of asphyxia, dopamine levels were increased to 130±12% in the ACC/TUB, and DOPAC levels were increased to 135±6% and 130±12% in the SN/VTA and the ACC/TUB, respectively. This suggests that the increased dopamine levels may preferably reflect an increased release of dopamine following perinatal asphyxia. In the 4-week-old rat, dopamine levels were decreased in the SN/VTA to 71±4%, in the striatum to 52±8%, and in the ACC/TUB to 53±7%, following 19–20 min of perinatal asphyxia as compared to controls. No changes were observed in DOPAC, HVA, or 3-MT levels, indicating that the reduced dopamine levels reflect a reduced dopamine synthesis following perinatal asphyxia. A decrease in dopamine utilization was observed in the striatum to 15±8% and in the ACC/TUB to 9±13% following 19–20 min of perinatal asphyxia as compared to controls. This indicates that perinatal asphyxia produced long-lasting reductions in activity in the mesostriatal/mesolimbic dopamine systems in the 4-week-old rat.
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  • 145
    ISSN: 1432-1017
    Keywords: Key words Gallstone ; Cholesterol monohydrate crystals ; Phase separation ; Light scattering ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Physics
    Notes: Abstract Phospholipid/cholesterol vesicles were solu-bilized by 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS). Above 30 mol% cholesterol (Ch) in the lipid vesicles several remarkable changes of the solubilization process were observed. (i) Two modes of solubilization: The effective detergent to lipid ratio Rc(M) for the formation of mixed micelles decreased from Rc(M) = 43 ± 3 at low lipid concentrations, [L]≤ 0.15 mm, to Rc(M) = 2.4 ± 0.3 above [L] = 0.5 mm (40 mol% Ch, T = 20 °C). (ii) At subsolubilizing CHAPS concentrations, filamentous and helical microstructures were formed, similar to those which were observed in native and model bile. (iii) The number of observed fibers was about two orders of magnitude higher in the presence of the negatively charged lipids phosphatidylglycerol (PG) and phosphatidic acid (PA) compared to the zwitterionic phosphatidylcholine (PC). Fiber formation began after 16–18 h using PG and PA compared to 3–4 days in the presence of PC. Screening of the charged lipids by NaCl effectively reduced the formation of fibers. Assuming binding of Na+ to the charged lipid aggregates, an intrinsic binding constant Kint = 0.6 M–1 was determined by applying the Gouy-Chapman theory. After the addition of CHAPS to PG/Ch vesicles, a fast initial solubilization of the vesicles (〈1 min) to mixed micelles (rh = 2.3 ± 0.2 nm) and small vesicles (rh = 23 ± 1 nm) was observed, followed by an intermediate period of 2 h, after which the formation of fibers occurred (〉15 h). The microstructures are visualized by darkfield and electron microscopy. The method of vesicle solubilization is compared to the dilution of concentrated micellar solutions, which is usually applied to model bile systems.
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  • 146
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    Biology and fertility of soils 21 (1996), S. 293-302 
    ISSN: 1432-0789
    Keywords: Key words Ammonium excretion ; Azorhizobium caulinodans ; Auxine ; 2 ; 4-Dichlor-phenoxy-acetic acid ; Nitrogen fixation ; Paranodulation ; Rice ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Geosciences , Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Rice seedlings developed nodule-like tumors (para-nodules) along primary and secondary roots when treated with the auxin 2,4-dichlor-phenoxy-acetic acid (2,4-D). Histologically, these tumors appeared as cancerous out-grown lateral-root primordes and were thus comparable with stem nodules of the legume Sesbania rostrata. Azorhizobium caulinodans (a diazotroph known as a specific endophyte of Sesbania rostrata) was introduced and became established inside rice para-nodules and in root tissues around tumor bases. The infection with A. caulinodans followed a typical “crack-entry” invasion at places where para-nodule tumors had emerged through the root cortex and epidermis. The bacteria settled with high cell densities in intercellular spaces of the induced tumors and betwen root cortical cells. Infection of plant cells took place both in the epidermis and in cortical tissue. Intracellularly established A. caulinodans was found inside the cytoplasm, surrounded by membrane-like structures. N2 fixation by tumor-inhabiting Azorhizobium sp. was increased at low O2 tensions (1.5–3 kPa) compared with an untreated control. Only a little activity remained at O2 tensions of 5 kPa and above. The present results confirm that root-tumor induction offers a suitable method of establishing diazotrophs endophytically in the roots of gramineous crops.
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  • 147
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    Biology and fertility of soils 21 (1996), S. 293-302 
    ISSN: 1432-0789
    Keywords: Ammonium excretion ; Azorhizobium caulinodans ; Auxine 2.4-Dichlor-phenoxy-acetic acid ; Nitrogen fixation ; Paranodulation ; Rice ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Geosciences , Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Rice seedlings developed nodule-like tumors (para-nodules) along primary and secondary roots when treated with the auxin 2,4-dichlor-phenoxy-acetic acid (2,4-D). Histologically, these tumors appeared as cancerous out-grown lateral-root primordes and were thus comparable with stem nodules of the legume Sesbania rostrata. Azorhizobium caulinodans (a diazotroph known as a specific endophyte of Sesbania rostrata) was introduced and became established inside rice para-nodules and in root tissues around tumor bases. The infection with A. caulinodans followed a typical “crack-entry” invasion at places where paranodule tumors had emerged through the root cortex and epidermis. The bacteria settled with high cell densities in intercellular spaces of the induced tumors and between root cortical cells. Infection of plant cells took place both in the epidermis and in cortical tissue. Intracellularly established A. caulinodans was found inside the cytoplasm, surrounded by membrane-like structures. N2 fixation by tumor-inhabiting Azorhizobium sp. was increased at low O2 tensions (1.5–3 kPa) compared with an untreated control. Only a little activity remained at O2 tensions of 5 kPa and above. The present results confirm that root-tumor induction offers a suitable method of establishing diazotrophs endophytically in the roots of gramineous crops.
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  • 148
    ISSN: 1432-0738
    Keywords: Key words L-2-Chloropropionic acid ; Glutathione ; Cerebellar granule cell necrosis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The role of glutathione (GSH) in the neurotoxicity produced following a single oral dose of 750 mg/kg L-2-chloropropionic acid (L-CPA) has been investigated in rats. L-CPA-induced neurotoxicity was characterised by up to 80–90% loss in cerebellar granule cells and cerebellar oedema leading to locomotor dysfunction. Neurochemically, L-CPA-induced neurotoxicity produced a reduction in the concentration of aspartate and glutamate in the cerebellum and a reduction in the density of NMDA receptors in the cerebellar cortex, whilst there was an increase in cerebellar glycine, glutamine and GABA concentrations. Treatment of rats with buthionine sulfoximine (BSO) at 1 g/kg, i.p., an inhibitor of GSH synthesis, potentiated the toxicity of L-CPA, such that many of the neurochemical markers were significantly different from controls at earlier time points, compared to animals which had received L-CPA alone, and toxicity was also seen in the kidney of BSO plus L-CPA treated rats. In contrast, supplementing GSH concentrations by administration of the isopropyl ester of glutathione (ip-GSH) at 1 g/kg, s.c., was able to protect rats against L-CPA neurotoxicity and prevent many of the neurochemical changes. In order to assess whether the depletion of GSH in the rat cerebellum following L-CPA treatment was related to the delivery of cysteine or cystine, the accumulation of [14C] cystine into cerebellar slices was characterised and found to be energy dependent, Na+ independent and obey saturation kinetics with an apparent Km of 77 μM and an apparent Vmax of 450 nmol/g wet weight per h. The accumulation of cystine into cerebellar slices was non-competitively inhibited by the cysteine conjugate of L-CPA with an apparent Ki of approximately 60 μM, whilst glutamate only inhibited cystine accumulation at doses which were cytotoxic to cerebellar slices. Hence the depletion of GSH in the rat cerebellum, following L-CPA administration, may be due to a reduction in the delivery to the brain of cysteine or cystine, one of the components required for GSH synthesis, by the cysteine conjugate of L-CPA. Our studies show the pivotal role GSH plays in cerebellar granule cell necrosis induced by L-CPA in the rat, indicating that a marked and sustained reduction in cerebellar GSH content by L-CPA may leave granule cells vulnerable to cytotoxic free radical damage leading to cell death, possibly mediated through excitatory amino acids.
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  • 149
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    Archives of toxicology 70 (1996), S. 474-481 
    ISSN: 1432-0738
    Keywords: Key words Quinolone (♪) ; Cartilage lesions ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The reversibility of quinolone-induced cartilage lesions has not been studied in detail. We treated five groups of five to seven juvenile Wistar rats (male and female; age: 5 weeks) with 2×600 mg ofloxacin/kg by gastric intubation on 1 day only (9:00 a.m. and 5:00 p.m.) and studied the knee joints histologically 3 days, 1, 3, 8 and 17 weeks later. In addition, joint cartilage specimens from vehicle-treated control rats (n=21) at corresponding age were examined. Cartilage lesions such as matrix swelling, loss of proteoglycans and horizontal clefts were found in nearly all knee joints (26 of 27 joints; incidence: 96%) of the ofloxacin-treated rats. Within the observation period of 4 months the size of these lesions in knee joint cartilage did not decrease significantly. The diameter of the lesions at the time points of evaluation was 1146±535, 1713±309, 1250 ±585, 1406±356, and 1542±467 μm, respectively (mean values±sd). Chondrocyte clusters producing glycosaminoglycans were observed 3 weeks after dosing and at later time points. They are considered to reflect the onset of repair but chondrocyte organization did not normalize during the study period, thus indicating the irreversibility of the effect under the experimental conditions. In principle, long-term joint cartilage damage has to be taken into account when the use of quinolones in children is considered. More detailed pharmacokinetic data are necessary for a reasonable risk assessment approach.
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  • 150
    ISSN: 1432-0738
    Keywords: Key words Cadmium ; Erythropoietin ; Anemia ; Rat ; Kidney
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Cadmium (Cd), a highly toxic heavy metal, is distributed widely in the general environment of today. The characteristic clinical manifestations of chronic Cd intoxication include renal proximal tubular dysfunction, general osteomalacia with severe pains, and anemia. We have recently reported that the serum level of erythropoietin (EPO) remained low despite the severe anemia in patients with Itai-itai disease, the most severe form of chronic Cd intoxication. In order to prove that the anemia observed in chronic Cd intoxication arises from low production of EPO in the kidneys following the renal injury, we administered Cd to rats for a long period and performed the analysis of EPO mRNA inducibility in the kidneys. The rats administered Cd for 6 and 9 months showed anemia with low levels of plasma EPO as well as biochemical and histological renal tubular damage, and also hypoinduction of EPO mRNA in the kidneys. The results indicate that chronic Cd intoxication causes anemia by disturbing the EPO-production capacity of renal cells.
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  • 151
    ISSN: 1432-0738
    Keywords: Key words Hexachlorobenzene ; Rat ; Operant behavior ; Gestation ; Liver
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Hexachlorobenzene (HCB) is still frequently found at elevated levels in human adipose tissue and breast milk. As intoxication with HCB causes neurological disturbance in human beings, the purpose of the present study was to examine neurobehavioral functions in rats after pre- and postnatal exposure. Female rats were fed diets with 0, 4, 8, or 16 mg HCB/kg diet. Exposure started 90 days prior to mating and was continued throughout mating, gestation, and lactation. Thereafter, the offspring were given the same diets as their respective mothers. HCB levels were determined in the brain, the liver, and in the adipose tissue from virgin rats, dams, and the offspring. Concentrations on a lipid basis were found to decline in the order adipose〉liver〉brain. The exposure levels chosen did not cause gross toxic effects in dams or offspring. There were dose-related increases in liver-to-body-weight ratios in exposed dams, but not in unmated females treated alike. Behavioral testing was conducted in the offspring. Examination of open-field activity on PND 21, and of active avoidance learning on PND 90 failed to reveal significant differences between groups. Training of operant behavior started at the age of 150 days in the offspring from the control, the 8-mg group, and the 16-mg group. Animals were trained on a fixed interval schedule of 1 min (FI-1). On this schedule, responses were reinforced by a food pellet every time 1 min had elapsed after the preceding reinforcement. There were dose-dependent reductions in the post-reinforcement pause, e.g. the time between each reinforcement and the first reaction emitted after it. In addition, the index of curvature, which describes the efficiency of performance on the FI-1 schedule, was decreased in a dose-dependent fashion.
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  • 152
    ISSN: 1432-0738
    Keywords: Key words Glutathione ; Glutathione-related enzymes ; Hepatocytes ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The effect of culture medium on glutathione (GSH) dependent detoxification defence system of primary cultured hepatocyte from either male or female rats was studied. Intracellular reduced (GSH) and oxidized glutathione (GSSG), and six GSH-related enzyme activities, including GSH peroxidase (GSH Px), GSH reductase (GSH Rd), cytosolic GSH S-transferase (cGST), microsomal GSH S-transferase (mGST), γ-glutamyl transpeptidase (GTP), and γ-glutamylcysteine synthetase (GCS), were investigated during a 6-day culture. Media free of fetal bovine serum (FBS) and with 2.5 or 10% FBS were used. Whatever the medium, there was an initial increase of intracellular GSH and GSSG, a threefold increase of GSH at day 3 and fourfold increase of GSSG at day 4, later decreasing to their original level at day 6. The activities of all six GSH-related enzymes of male and female hepatocytes remained relatively stable during the first 72 h, then gradually decreased to 50–80% of initial activities. With the exception of cGST, time-course profiles of other enzyme activities were not significantly different among various media. In both sexes, higher cGST activity was maintained for cells cultured in the presence of FBS. Results of immunoblotting analysis of cytosolic GST isozymes indicate that the placental form of GST (Yp) was markedly increased after plating and the extent of increase of Yp was higher in the presence of FBS. Despite the culture medium, the level of GST isoform Ya was maintained steadily for 6 days, however, Yb was maintained during the first 3 days and then decreased. In terms of the gender difference, GSH Px and GTP activities of hepatocytes from females were significantly greater than of males over the entire culture period. Results indicate that FBS seems not to be absolutely essential in maintaining GSH level and most of the GSH-related enzyme activities in rat hepatocytes. Furthermore, GSH levels and GSH-related enzyme activities of hepatocytes from female rats were similar to those from male rats.
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  • 153
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    Archives of toxicology 70 (1996), S. 310-314 
    ISSN: 1432-0738
    Keywords: Key words Methylmercury ; Mercury ; Placenta ; Neutral amino acid ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Methylmercury (MeHg) penetrates the placental barrier to affect developing fetuses in the uterus. However, the mechanism of placental MeHg transport is not well defined. To clarify the MeHg transport system that functions in the placenta, pregnant rats were intravenously administered MeHg on day 18 of gestation. The fetal blood was collected from the umbilical cord at 30 and 60 min after the administration, and its mercury concentration was measured. MeHg was found to be rapidly transported to the fetal blood in a time- and dose-dependent manner, and predominantly distributed in the blood cells there. MeHg transport was effectively suppressed by the co-injection of neutral amino acids, i.e., L-methionine and L-phenylalanine, suggesting that MeHg is actively transported as its cysteine conjugate via the neutral amino acid carrier system. The suppression by methionine was not so marked as by phenylalanine. Since methionine administration caused a rapid increase of the cysteine, which functioned as a predominant carrier in MeHg transport, in the maternal plasma, newly synthesized cysteine seemed to accelerate the mercury uptake. Accordingly, the acceleration by the extra cysteine would compensate partly the competitive effect of methionine as a neutral amino acid.
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  • 154
    ISSN: 1432-0738
    Keywords: Key words Formaldehyde ; Acrolein ; Acetaldehyde ; Rat ; Sensory irritation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Sensory irritation of formaldehyde (FRM), acrolein (ACR) and acetaldehyde (ACE) as measured by the decrease in breathing frequency (DBF) was studied in male Wistar rats using nose-only exposure. Groups of four rats were exposed to each of the single compounds separately or to mixtures of FRM, ACR and/or ACE. Exposure concentrations of the mixtures were chosen in such a way that summation of the effects of each chemical would be expected not to exceed 80% reduction of the breathing frequency. FRM, ACR and ACE appeared to act as sensory irritants as defined by Alarie (1966, 1973). With FRM and ACR desensitization occurred, whereas with ACE the breathing frequency gradually decreased with increasing exposure time (up to 30 min). For mixtures, the observed DBF was more pronounced than the DBF for each compound separately, but was less than the sum of the DBFs for the single compounds. A model for three compounds competing for the same receptor was applied to predict the DBF of mixtures of FRM, ACE and ACR. The results also showed that with mixtures no desensitization occurred; in fact, the breathing frequency further decreased in the last 15 min of exposure. These observations were similar to those found for ACE alone, and might have been caused by effects on the upper respiratory tract. The results of the present study allow the conclusion that sensory irritation in rats exposed to mixtures of irritant aldehydes is more pronounced than that caused by each of the aldehydes separately, and that the DBF as a result of exposure to a mixture could well be predicted using a model for competitive agonism, thus providing evidence that the combined effect of these aldehydes is basically a result of competition for a common receptor (trigeminal nerve).
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  • 155
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    Archives of toxicology 70 (1996), S. 368-372 
    ISSN: 1432-0738
    Keywords: Key words Phenobarbital ; 2-Aminoisobutyric acid ; Hepatoytes ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Phenobarbital (PB) is a classical inducer of drug metabolizing enzymes and known to stimulate liver growth transiently in rodents. Previous studies have shown that regenerative liver growth after a partial hepatectomy is accompanied by the induction of the amino acid transport system A. In the present study we investigated whether amino acid transport is also increased by treatment of rats with PB. Na+-dependent hepatic uptake of the non-metabolizable amino acid 2-aminoisobutyric acid (AIB), which proceeds largely via transport system A, was studied in isolated hepatocytes from PB treated and untreated rats. Uptake of AIB (100 μM) was maximally induced (2.5-fold) 8 h after the beginning of PB treatment. Within 4 days, transport rates decreased to values similar to those determined in hepatocytes from untreated animals, despite the continuation of PB treatment. In contrast, induction of the PB-inducible cytochromes P450 2B1/2 was markedly increased during the entire experiment, as determined with the isoenzyme-selective substrate pentoxyresorufin. Kinetic analysis of AIB uptake revealed a “high” and a “low” affinity transport system. It is most likely that the high affinity system represents amino acid transport system A. Treatment with PB increased the Vmax value but did not affect the apparent Km value of the high affinity system. The present data suggest that the hepatic mitogen PB transiently induces amino acid transport system A.
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  • 156
    ISSN: 1432-1076
    Keywords: Key words Rhizomelic ; chondrodysplasia punctata ; Dihydroxyacetonephosphate-acyl-transferase ; Electron microscopy ; Peroxisomes ; Morphometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rhizomelic chondrodysplasia punctata (RCDP) is clinically characterized by symmetrical shortening of the proximal limbs, contractures of joints, a characteristic dysmorphic face, and cataracts. In the classical form an impairment of several peroxisomal functions and enzymes (plasmalogen synthesis, phytanic acid oxidation, 3-oxoacyl-CoA thiolase) has been repeatedly shown. Recently a variant involving only the peroxisomal dihydroxyacetonephosphate acyltransferase (DHAP-AT) has been described. We present a patient with isolated DHAP-AT deficiency and all clinical, radiological, and pathological features of classical RCDP. For the first time, microscopy and immunocytochemistry of hepatocytes could be performed. Conclusion In contrast to studies on classical rhizomelic chondrodysplasia punctata which have shown enlarged peroxisomes in numbers varying from hepatocyte to hepatocyte, the peroxisomes in our patient seem to be normal in size, number and shape.
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  • 157
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    Archives of microbiology 166 (1996), S. 357-360 
    ISSN: 1432-072X
    Keywords: Key wordsEscherichia coli ; Capsule ; Serotype ; Edema disease ; Electron microscopy ; Cell adhesion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The fine structure of the cell surface of seven enterotoxemic Escherichia coli (ETEEC) O139:K12 strains isolated from piglets with edema disease were examined electron microscopically using both the negative-staining method and the freeze-substitution fixation method. Densely packed, fine fibers were observed; they consisted of a capsule layer approximately 25 nm thick around the cell surfaces of strains 107/86, IW-2, ED-3, ED-43, and ED-61, all of which have a capacity to adhere strongly to HEp-2 cells. In contrast, no such structure was observed on the surface of strains RK-O139 or ED-1, both of which adhere only weakly to HEp-2 cells. These results suggest that the capsule structure might be associated with the ability to adhere to HEp-2 cells and, as a result, also potentially play some role in ETEEC infection.
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  • 158
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    Surgical endoscopy and other interventional techniques 10 (1996), S. 490-494 
    ISSN: 1432-2218
    Keywords: Laparoscopy ; Rat ; Tumor take ; Weight loss ; Pneumoperitoneum ; Bowel resection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: The ability of laparoscopic techniques to treat malignant disease is controversial. We developed a rat model to assess metabolic and oncological effects of laparoscopic surgery. Methods: Experiment I. The postoperative body weight in 10 rats having laparoscopic bowel resection (group I), 10 rats having open bowel resection (group II) and 5 rats having anesthesia only (group III) was determined. Experiment II. Tumor take was scored in 11 rats having laparoscopic bowel resection (group IV), 11 rats having open bowel resection (group V), 6 rats having CO2 pneumoperitoneum without bowel resection (group VI) and 6 rats having anesthesia only (group VII). All rats had CC531 cancer cells injected intraperitoneally postoperatively. Results: Experiment I. Body weight loss in group I compared to group II (p〈0.036). Rats of group III lost no weight postoperatively. Experiment II. Tumor take was less in the subcutis (p=0.005), parietal peritoenum (p〈0.001) and bowel anastomosis (p=0.021) in group IV compared to group V. Tumor take was significantly greater at all sites except for subcutis in group VI compared to VII (all p〈0.022). Conclusions: Laparoscopic surgery is associated with less postoperative weight loss and less tumor take compared to open surgery. CO2 insufflation appears to increase tumor take.
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  • 159
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    Psychopharmacology 123 (1996), S. 98-102 
    ISSN: 1432-2072
    Keywords: Sucrose ; Raclopride ; 5-HT2 antagonism ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We examined the effects on sucrose consumption of a dopamine (DA) D2/D3 antagonist (raclopride, 0–0.3 mg/kg), a serotonin 5-HT2/2c antagonist (ritanserin, 0–0.4 mg/kg), and raclopride (0.15 mg/kg) combined with ritanserin (0–0.4 mg/kg). Three different concentrations of sucrose solution (0.7%, 7.0% and 34%) were tested. The concentration-intake function in drug-free rats was an inverted-U, with 7.0% sucrose supporting the highest intake. Raclopride (0.3 mg/kg) inhibited intake of 7.0% sucrose, but its effect on 0.7% sucrose fell short of significance (P〈0.06) and intake of 34% sucrose was unchanged. Ritanserin did not affect sucrose intake when given on its own, but synergized with a previously ineffective dose of raclopride (0.15 mg/kg) so as to cause a significant inhibition of 7.0% sucrose intake and increase in 34% sucrose intake. These data indicate that 5-HT2 antagonism potentiated the behavioural effects of raclopride and we speculate that this interaction might contribute to the efficacy of atypical neuroleptic drugs.
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  • 160
    ISSN: 1432-2072
    Keywords: 2,4-Dithiobiuret ; Rat ; Cognitive facilitation ; Motor impairment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 2,4-Dithiobiuret (DTB) is a sulfonated derivative of urea that is used as a reducing agent in chemical manufacture. Its low acute toxicity to rodents belies a peripherally mediated, delayed-onset muscle weakness which develops during repeated daily exposure. In experiment 1, a standard dose regimen of DTB (0.5 mg/kg per day IP for 5 days) was used to induce motor dysfunction as a way to dissociate peripheral and central influences on a test of cognitive and motor function in rats. Sixteen male rats were trained to perform a Delayed Matching-to-Position/Visual Discrimination (DMTP/VD) task which permits quantification of working memory (matching accuracy), reference memory (discrimination accuracy), and motor function (choice response latency and nosepoke inter-response time, IRT). The first dose of DTB significantly increased matching accuracy; during the following week, DTB reduced matching accuracy, increased choice response latency and nosepoke IRT, and reduced trial completion. Discrimination accuracy remained unaffected. Experiment 2 explored the effects of single administrations of DTB on DMTP/VD. Sixteen other trained rats were divided into two groups with equal matching accuracy. One group received DTB (0.5,1.0, and 2.0 mg/kg, IP) in separate injections at least 1 week apart; the other group received vehicle at the same times. Matching accuracy increased significantly in the treated rats and not in the controls following each dose of DTB. The magnitude of this increase was dose-dependent, and lasted from 1 to 8 weeks after each injection. Discrimination accuracy, response latency, nosepoke IRT and trial completion remained unaffected throughout the study. After DTB, matching accuracy was less easily disrupted by scopolamine (0.1–0.3 mg/kg, IP). However, DTB did not alter the rats' response to reducing the distance between the response levers, to reversal of the matching rule to a nonmatching rule, or to challenge with MK-801 (0.05–0.10 mg/kg, IP). These data indicate that acute DTB causes a long-lasting facilitation of working memory in rats in the absence of any of the indications of motor impairment which follow repeated, daily injections of the chemical.
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  • 161
    ISSN: 1432-2072
    Keywords: Key words Thyrotrophin-releasing hormone ; RX77368 ; Alzheimer’s disease ; AMPA ; Septal-hippocampal ; Working memory ; Delayed non-matching to position (DNMTP) ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of the present study was to determine the effect of a thyrotrophin-releasing hormone (TRH) analogue, RX77368, on performance of a working memory test, using a delayed non-matching to position (DNMTP) procedure, in (RS)-α-amino-3-hydroxy- 5-methyl-4-isoxazolepropionic acid (AMPA)-induced septal-hippocampal lesioned rats. Following a post-surgery recovery period, pretrained rats were tested once daily on DNMTP, 30 min post-administration of RX77368 (1.0 mg kg–1, IP) or saline. AMPA-induced lesions significantly reduced percent correct responses during the second week of testing. Comparison of percent correct responses between days 1 and 13 of testing showed that sham rats significantly improved DNMTP performance, whereas lesioned rats did not. RX77368 significantly reduced general locomotor activity in sham rats in activity boxes, but did not disrupt non-mnemonic measures, such as locomotion and motivation, in the DNMTP test. RX77368 increased percent correct responses in AMPA-lesioned rats on days 8–10 and 11–13. There was also a significant improvement in percent correct responses achieved between day 1 and 13 in RX77368-treated lesioned and sham rats. These results showed that: (i) septal-hippocampal lesioned rats did not improve over the testing period; and (ii) on test days when a significant impairment was present, RX77368 partially improved DNMTP performance.
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  • 162
    ISSN: 1432-2072
    Keywords: Key words Opioids ; Tolerance ; Neurotensin ; NMDA ; Conditioning ; MK-801 ; Morphine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Opiate tolerance involves both associative and non-associative changes. However, procedures designed to distinguish between these two processes have rarely been employed when investigating the physiological basis of such plasticity. The present experiments assessed some of the mechanisms contributing to both associative and non-associative decreases in morphine analgesic potency following repeated IV morphine administration (4 days, 5 mg/kg per day). For one group of rats, testing for morphine analgesia (tailflick) occurred in a context that had been repeatedly paired with morphine administration. Another group of rats, exposed equally to the testing context, handling procedures and morphine, was tested for morphine analgesia in a context that was specifically unpaired with prior drug. Although both of these groups showed a decrease in the drug effect following repeated administrations, those rats tested in the morphine-associated context were significantly more tolerant than the unpaired group. We evaluated the spinal cord involvement of NMDA receptors, as well as the peptide neurotensin in these two types of tolerance. NMDA receptors appeared to mediate non-associative changes in drug potency, as rats tested in either context were less tolerant when morphine administration was preceded with the non-competitive NMDA antagonist, MK-801 (2.5 and 5 nmol). Spinal neurotensin antagonism with [d-Trp11]neurotensin (3 pmol) selectively abolished associative tolerance. These findings provide information about the mechanisms of opiate tolerance and support the distinction between associative and non-associative processes underlying these changes.
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  • 163
    ISSN: 1432-2072
    Keywords: Alzheimers' disease ; α2-Adrenoceptor antagonists ; Acetylcholinesterase inhibitor ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The cholinergic hypothesis of Alzheimer's disease (AD) has strongly influenced research on learning and memory over the last decade. However, there has been limited success treating AD dementia with cholinomimetics. Furthermore, there are indications that other neurotransmitter systems affected by this disease may be involved in cognitive processes. Animal studies have suggested that norepinephrine and acetylcholine may interact in learning and memory. The current experiments investigate this interaction in a step-down passive avoidance paradigm after coadministration of acetylcholinesterase inhibitors and α2-adrenoceptor antagonists. Administration of acetylcholinesterase inhibitors heptylphysostigmine (0.625–5.0 mg/kg, IP), tacrine (2.5–10.0 mg/kg, PO), velnacrine (0.312–2.5 mg/kg, SC), and galanthamine (0.312–2.5 mg/kg, IP) each enhanced retention of a passive avoidance response at selected moderate doses administered 30–60 min prior to training. The α2-adrenoceptor antagonists idazoxan (0.312–2.5 mg/kg, IP), yohimbine (0.078–0.312 mg/kg, IP) and P86 7480 (0.156–0.625 mg/kg, IP) alone failed to enhance learning in this paradigm. Coadministration of a subthreshold dose of heptylphysostigmine (0.625 mg/kg, IP) with doses of idazoxan, yohimbine or P86 7480 enhanced passive avoidance learning. This synergistic interaction may represent effects of antagonism of presynaptic α2-adrenoceptor since coadministration of heptylphysostigmine and the selective postsynaptic α2-adrenoceptor antagonist SKF104856 did not result in enhanced learning. Taken together these data suggest noradrenergic activation through pre-synaptic α2-adrenoceptor blockade may potentiate cholinergic activity in the formation of a long-term memory trace. These observations may have implications for the treatment of AD with cholinergic and adrenergic agents.
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  • 164
    ISSN: 1432-2072
    Keywords: Social recognition ; Memory ; Rat ; Mouse ; Cannabimimetic ; Cannabinoid antagonist ; SR 141716 ; Ageing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Social short-term memory in rodents is based on the recognition of a juvenile by an adult conspecific when the juvenile is presented on two successive occasions. Cannabimimetics are claimed to induce memory deficits in both humans and animals. In the brain, they mainly bind to CB1 receptors for which anandamide is a purported endogenous ligand. SR 141716, a specific antagonist of CB1 receptors, dose-dependently reverses biochemical and pharmacological effects of cannabimimetics. More particularly, it antagonizes the inhibition of hippocampal long-term potentiation induced by WIN 55,212-2 and anandamide, and it increases arousal when given alone. The present experiments study the ability of SR 141716 (from 0.03 to 3 mg/kg SC) to facilitate short-term olfactory memory in the social recognition test in rodents. SR 141716 improved social recognition in a long intertrial paradigm with a threshold dose of 0.1 mg/kg SC. At 1 mg/kg, it antagonized the memory disturbance elicited by retroactive inhibition. Scopolamine (0.06 mg/kg IP) partially reversed its memory-enhancing effect. Moreover, SR 141716 reduced memory deficit in aged rats (0.03–0.1 mg/kg) and mice (0.3–1 mg/kg). As SR 141716 is not known to exhibit any pharmacological activity which is not mediated by CB1 receptors, the results strongly support the concept that blockade of CB1 receptors plays an important role in consolidation of short-term memory in rodents and suggest there may be a role for an endogenous cannabinoid agonist tone (anandaminergic) in forgetting.
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  • 165
    ISSN: 1432-2072
    Keywords: SKF 38393 ; Quinpirole ; SCH 23390 ; l-Sulpiride ; Nucleus accumbens shell ; Nucleus accumbens core ; Turning behaviour ; Dopamine D1 and D2 receptors ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The goal of this study was to determine whether dopamine D2 and/or D1 receptors in the shell and the core of the nucleus accumbens of rats have a differential role in turning behaviour. Unilateral injection of a mixture of the dopamine D2 receptor agonist quinpirole (10 µg) and the dopamine D1 receptor agonist 1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7, 8-diol (SKF 38393, 5 µg) into the shell of the nucleus accumbens produced contralateral turning, when doses which per se were ineffective were injected. This effect was far greater than that found after similar injections into the core of the nucleus accumbens. The effect elicited from the shell was significantly attenuated by prior administration of either the dopamine D2 receptor antagonistl-sulpiride (25 ng/0.5 µl) or the dopamine D1 receptor antagonist (8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-ol (SCH 23390, 0.5 µg/0.5 µl) into the same region. These data together with the fact thatl-sulpiride is known to be a valid tool to differentiate the involvement of distinct regions within the shell underlie the conclusion that dopamine D2 and D1 receptors in the shell, but not the core, of the nucleus accumbens play a critical role in the contralateral turning induced by unilateral injection of dopamine receptor agonists into this nucleus. The results are discussed in view of the known output pathways of the shell.
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  • 166
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    Psychopharmacology 126 (1996), S. 286-292 
    ISSN: 1432-2072
    Keywords: Modafinil ; Ephedrine ; Cocaine ; Amphetamine ; Self-administration ; Drug discrimination ; Rhesus monkey ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Modafinil [(diphenyl-methyl)sulphinyl-2-acetamide] is a novel psychostimulant drug which is effective in the treatment of narcolepsy and idiopathic hypersomnia. It also has neuroprotective effects in animal models of striatal neuropathology. Although the cellular mechanisms of action of modafinil are poorly understood, it has been shown to have a profile of pharmacological effects that differs considerably from that of amphetamine-like stimulants. There is some evidence that modafinil has central α1-adrenergic agonist effects. In the present study modafinil was evaluated for cocaine-like discriminative stimulus effects in rats and for reinforcing effects in rhesus monkeys maintained on intravenous cocaine self-administration. Modafinil,l-ephedrine andd-amphetamine all produced dose dependent increases in cocaine-lever responding, with maximal levels of 67%, 82% and 100%, respectively. Modafinil produced full substitution in four out of the six rats tested while the highest levels of substitution were associated with substantial response rate decreasing effects. Little evidence was obtained that the discriminative stimulus effects of modafinil were produced by α1-adrenergic activation, based upon results of tests performed in combination with prazosin. In the self-administration procedure, modafinil andl-ephedrine functioned as reinforcers in rhesus monkeys. The reinforcing and discriminative stimulus effects of modafinil required very high doses: modafinil was over 200 times less potent thand-amphetamine and was also less potent thanl-ephedrine. These results show that modafinil has some cocaine-like discriminative stimulus effects and, like other abused stimulants, can serve as a reinforcer at high doses.
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  • 167
    ISSN: 1432-2072
    Keywords: Dorsal raphe nucleus ; Rat ; WAY-100635 ; 8-OH-DPAT ; Somatodendritic 5-HT1A receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the rat shock-induced ultrasonic vocalization test, the anxiolytic effects of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) obtained after systemic (IP) and intracerebral injection into the dorsal raphe nucleus (DRN) were selectively abolished by pretreatment with the 5-HT1A receptor antagonist WAY-100635 [N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclo-hexanecarboxamide trihydrochloride]. This blockade was demonstrated both after systemic and DRN application of WAY-100635. Therefore, it is concluded that the anxiolytic effects of 8-OH-DPAT are mediated by activation of somatodendritic 5-HT1A receptors.
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  • 168
    ISSN: 1432-2013
    Keywords: Central chemoreceptors ; Peripheral chemoreceptors ; Fos ; Rat ; Hypercapnia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Exposure to hypercapnia and electrical stimulation of the carotid sinus nerve (CSN) has been shown to induce c-fos expression in several brain stem regions including the nucleus tractus solitarius (NTS). To test whether the labeled neurons were activated directly by hypercapnia or secondarily via the carotid bodies (sinus nerve), adult rats were exposed to either air or 14–16% CO2 for 1 h. Experiments were done on eight groups: (1) exposure to air, (2) exposure to CO2, (3) chronic CSN denervation/CO2, (4) chronic unilateral CSN denervation/CO2, (5) chronic sham CSN denervation/CO2, (6) anesthetized/CO2, (7) anesthetized and acute vagotomy/CO2, and (8) premedicated with morphine, 10 mg s.c., 20 min before exposure to CO2. After exposure to CO2 or air the rats were anesthetized, perfused with 4% paraformaldehyde and the brains processed for immunohistochemical staining for c-fos protein using the PAP (i.e. peroxidase anti-peroxidase) technique. Labeled neurons in the area of the NTS in every second 50-μm section were counted and their position plotted using a microscope and camera lucida attachment. Rats exposed to CO2 had a significantly greater number of labeled neurons in the NTS than those exposed to air. Other interventions, such as CSN denervation, surgery, anesthesia, vagotomy or injection of morphine did not significantly affect the level of c-fos expression in rats exposed to hypercapnia, indicative of central stimulation rather than secondary peripheral input. These responsive neurons may be part of a widespread central chemoreceptive complex.
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  • 169
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    Pflügers Archiv 431 (1996), S. 882-887 
    ISSN: 1432-2013
    Keywords: Key words Contractile ; Staircase ; Calcium ; Rat ; Fast-twitch ; Fatigue
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Myosin light chain (P-LC) phosphorylation, which is thought to be the principle mechanism for twitch potentiation in skeletal muscle, is significantly decreased during staircase in fatigued muscle. Attenuated phosphorylation of P-LC could be due to either depressed Ca2+ transients in fatigue, or to some inhibitory influence of contractile activity on myosin light chain kinase (MLCK). Tetanic stimulation, which would presumably result in maximal activation of MLCK, could be used to evaluate these potential mechanisms. P-LC phosphorylation and twitch developed tension (DT) were assessed at 20 and 120 s following a tetanic contraction in either rested or fatigued rat gastrocnemius muscle in situ. P-LC phosphorylation was significantly lower in fatigued muscles (39.7 ± 3.2% vs 54.8 ± 3.5%, 20 s after a 2-s tetanic contraction), while posttetanic potentiation (PTP) was similar in fatigued (189.1 ± 6.5%) versus rested muscle (169.5 ± 2.6%). Tetanic DT was reduced following the fatigue protocol and, thus, the assumption that the MLCK system was fully activated by Ca2+ may not be valid. The potentiation-phosphorylation relationships were linear for both rested and fatigued muscles; however this relationship was shifted markedly leftward in fatigued muscles. It appears that during PTP, equivalent potentiation is attained with correspondingly lower levels of P-LC phosphorylation in fatigued muscle. This enhanced relative potentiation for a given level of phosphorylation could be expected if Ca2+ transients were attenuated in the fatigued muscle. However the results do not rule out the possibility that other factors contribute to potentiation under these circumstances.
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  • 170
    ISSN: 1432-2013
    Keywords: Key words Hypobaric hypoxia ; Physical training ; Skeletal muscle ; Muscle fibre type ; Fibre cross-sectional area ; Enzymes of energy metabolism ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Adaptations of skeletal muscle morphology and metabolic enzymes were studied after prolonged training in and exposure to hypobaric (740 –770 mbar) as well as normobaric conditions in rats performing treadmill running training for 10, 21 and 56 days. Animals sacrificed after 91 days served as recovery groups from training and hypobaric exposure for 56 days. The rats were divided into normobaric sedentary (NS) and training (NT) groups and hypobaric sedentary (HS) and training (HT) groups. The weights of extensor digitorum longus (EDL) and soleus (SOL) muscles increased significantly in the 56HS and the 56HT groups compared with the 56NS group, the increase being greatest in the 56HS group. No differences in the mean fibre areas (MFA) of these muscles could be seen, whereas clearly reduced MFAs of type IIA and IIB were observed in the tibialis anterior (TA) muscle. However, fibre area distribution analyses in the EDL and TA muscles showed a higher proportion of larger fibers in the 56HS and 56HT groups than in the respective normobaric groups. On the contrary, in SOL muscles the proportion of smaller fibers was higher in the hypobaric than in normobaric groups at 56 days. Increased activities of citrate synthase and β-hydroxyacyl-CoA-dehydrogenase in SOL and TA muscles in the 56HT group indicate an increase in oxidative capacity. It is concluded that exposure to, and training in moderate hypobaric conditions leads to a positive muscle protein balance which is reflected in increased muscle weights. However, the sites of increased protein synthesis and the possible hyperplasia remain to be studied further.
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  • 171
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    Pflügers Archiv 432 (1996), S. 313-319 
    ISSN: 1432-2013
    Keywords: Key words Soleus muscle ; Rat ; Atrophy ; Unloading ; Motor units ; Contractile properties
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purpose of this study was to compare the isometric contractile properties of rat soleus motor units after 14 days of hindlimb unloading (HU) to those under control conditions. The motor units (MU) were classified using two mechanical criteria: the presence or not of a sag during unfused tetani and the value of the twitch time-to-peak (TTP). Under control conditions, the soleus muscle was composed of 85% of slow-type (sag −, TTP 〉 20 ms) and 15% of fast-type (sag +, TTP 〈 20 ms) units. Following HU, these two populations were still present and results showed: (1) large decreases in their maximal tetanic tensions (of −67% and −60% for slow- and fast-type, respectively), and (2) changes in their relative proportions, i.e. a decrease in the percentage of slow-type units and a twofold increase in the percentage of fast-type units were observed. These latter changes might be the consequence of a complete transformation of slow-towards fast-type units. A third population appeared in the HU solei, 26% of the samples, combining the presence of a sag and speed-related properties between those of slow- and fast-type units. These slow-intermediate units might come from slow units partially transformed into a faster type during HU. Thus the present study showed that unloading conditions induced a reorganisation of the soleus motor unit profile. The complete or partial transformation of the motor units could be related to the changes in the electromyographical activity of the unloaded soleus.
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  • 172
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    Pflügers Archiv 431 (1996), S. 775-785 
    ISSN: 1432-2013
    Keywords: Rat ; Pancreas ; RIN cells ; Gap junctions ; Connexin43 ; Biophysical properties ; Voltage gating
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A communication-deficient cell line (RIN cells, derived from a rat islet tumour), stably transfected with cDNA coding for rat connexin43 (Cx43), was chosen to further assess the mechanism of voltage gating of Cx43 gap junction channels. The experiments were carried out on preformed cell pairs using a dual whole-cell, voltage-clamp method. The junctional current,I j, revealed a time- and voltage-dependent inactivation at transjunctional voltagesV j 〉 ± 40mV When an asymmetrical pulse protocol was used (in cell 1 the holding potential was maintained, in cell 2 it was altered to establish a variableV j), the channels exhibited an asymmetrical gating behaviour:V j,O = −73.7 mV and 65.1 mV for negative and positiveV j, respectively (V j at whichI j is half-maximally inactivated); gj(min) = 0.34 and 0.29 (normalized minimal conductance); τ = 350 ms and 80 ms atV j = 100 mV (time constant ofI j inactivation). Hence, these parameters were more sensitive to positiveV j values. When a symmetrical pulse protocol was used (the holding potentials in cell 1 and cell 2 were altered simultaneously in steps of equal amplitude but of opposite polarity), theV j —dependent asymmetries were absent:V j,O = −60.5 and 59.5; gj (min) = 0.27 and 0.29; τ = 64 ms and 47 ms at 100 mV Putative explanations for these obervations are discussed. A possibility is that the number of channels alters with the polarity ofV j.
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  • 173
    ISSN: 1432-2013
    Keywords: Key words Central chemoreceptors ; Peripheral chemoreceptors ; Fos ; Rat ; Hypercapnia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Exposure to hypercapnia and electrical stimulation of the carotid sinus nerve (CSN) has been shown to induce c-fos expression in several brain stem regions including the nucleus tractus solitarius (NTS). To test whether the labeled neurons were activated directly by hypercapnia or secondarily via the carotid bodies (sinus nerve), adult rats were exposed to either air or 14–16% CO2 for 1 h. Experiments were done on eight groups: (1) exposure to air, (2) exposure to CO2, (3) chronic CSN denervation/CO2, (4) chronic unilateral CSN denervation/CO2, (5) chronic sham CSN denervation/CO2, (6) anesthetized/CO2, (7) anesthetized and acute vagotomy/CO2, and (8) premedicated with morphine, 10 mg s.c., 20 min before exposure to CO2. After exposure to CO2 or air the rats were anesthetized, perfused with 4% paraformaldehyde and the brains processed for immunohistochemical staining for c-fos protein using the PAP (i.e. peroxidase anti-peroxidase) technique. Labeled neurons in the area of the NTS in every second 50-μm section were counted and their position plotted using a microscope and camera lucida attachment. Rats exposed to CO2 had a significantly greater number of labeled neurons in the NTS than those exposed to air. Other interventions, such as CSN denervation, surgery, anesthesia, vagotomy or injection of morphine did not significantly affect the level of c-fos expression in rats exposed to hypercapnia, indicative of central stimulation rather than secondary peripheral input. These responsive neurons may be part of a widespread central chemoreceptive complex.
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  • 174
    ISSN: 1432-2013
    Keywords: Nerve graft ; Magnification ; Motor nerve conduction velocity ; Compound muscle action potential ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Controversy surrounds the value of optic magnification for peripheral nerve surgery. The aim of this study was to compare the loupe magnification with microscope-assisted techniques in a rat tibial nerve graft model. The parameters studied included motor nerve conduction velocity (MNCV), clinical test equivalent (CTE), soleus muscle weight (SMW) and morphometric nerve indices. In the loupe and microscope groups MNCV mean was 26.77 ± 9.37 m/sec and 44.19 ± 11.36 m/sec respectively. MNCV results suggest better regeneration in the microscope group, as confirmed by CTE, SMW and myelinated fibre (MF) diameter.
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  • 175
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    Pflügers Archiv 433 (1996), S. 166-173 
    ISSN: 1432-2013
    Keywords: Key words Action potential ; Fatigue ; Ischaemia ; Muscle fibres ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The proximal and distal compartments of rat medial gastrocnemius muscle are dominated, respectively by, fast-twitch oxidative and fast twitch glycolytic fibres. In the present study it was hypothesized that repetitive in situ activation with an intact blood supply would cause greater declines in maximal tetanic force, compound action potential (CAP) amplitude and CAP area in the distal compared to the proximal compartment. Furthermore, it was hypothesized that these differences would be eliminated after occlusion of the blood supply to the muscle. A twitch followed by a tetanus (120 Hz, 200 ms duration) was given every 3 s for 2 min. This exercise protocol was applied once with, and once without, blood supply. During the first minute of the exercise, as expected, occlusion enhanced the decline of proximal force to 77.4 ± 0.8%, a level comparable (P〉0.05) to the decline of distal force (79.7 ± 1.2%). In contrast with the hypothesis, CAP amplitude was not significantly affected by occlusion and it changed significantly less in the proximal (to 102.9 ± 4.5%) compared to the distal (to 69.0 ± 6.7%) compartment. During the second minute of activation without blood flow, sudden declines of distal CAP amplitude (to 18.4 ± 3.4%) coupled with parallel declines in force (to 17.6 ± 2.8%) were observed to occur in the distal but not in the proximal compartment. Proximal final force and CAP amplitude were 54.2 ± 2.6% and 80.6 ± 5.9% respectively. Thus, in contrast with the hypothesis, occlusion enhanced the differences between compartments. These results are discussed in relation to fibre type composition and metabolic changes. It is suggested that a loss of force caused by a decreased muscle fibre excitability upon repetitive activation depends not only on fibre type, but also on the intramuscular location of the fibres.
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  • 176
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    Bioscience reports 16 (1996), S. 159-187 
    ISSN: 1573-4935
    Keywords: Electron microscopy ; photosystem II ; thylakoid membrane
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract This review covers the recent progress in the elucidation of the structure of photosystem II (PSII). Because much of the structural information for this membrane protein complex has been revealed by electron microscopy (EM), the review will also consider the specific technical and interpretation problems that arise with EM where they are of particular relevance to the structural data. Most recent reviews of photosystem II structure have concentrated on molecular studies of the PSII genes and on the likely roles of the subunits that they encode or they were mainly concerned with the biophysical data and fast absorption spectroscopy largely relating to electron transfer in various purified PSII preparations. In this review, we will focus on the approaches to the three-dimensional architecture of the complex and the lipid bilayer in which it is located (the thylakoid membrane) with special emphasis placed upon electron microscopical studies of PSII-containing thylakoid membranes. There are a few reports of 3D crystals of PSII and of associated X-ray diffraction measurements and although little structural information has so far been obtained from such studies (because of the lack of 3D crystals of sufficient quality), the prospects for such studies are also assessed.
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  • 177
    ISSN: 1432-2072
    Keywords: Nicotine ; Lobeline ; Stimulus discrimination task ; Cognition ; Memory ; Cholinergic ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study evaluated the effects of two central nicotinic-cholinergic receptor agonists and an antagonist on performance accuracy of a rat, delayed stimulus discrimination task (DSDT). Rats were trained to discriminate between an auditory and visual stimulus by pressing a right or left lever. To diminish the rat's ability to use mediating spatial strategies to solve the task, computer automated, retractable doors separated the animal from the levers during delay intervals, thus reducing positioning at the lever. After stable baselines were achieved, rats were grouped and administered placebo (saline) and nicotine, lobeline or mecamylamine in a randomized dose series. Each group received two complete series of the selected compound on different occasions. Mecamylamine impaired DSDT accuracy in a dose-dependent manner while optimal doses of nicotine and lobeline significantly improved accuracy. Nicotine differed from lobeline in regard to its interaction with a dose of mecamylamine (1.0 mg/kg) that had not impaired DSDT accuracy. Combined administration of lobeline and mecamylamine was followed by a significantly increased level of DSDT accuracy that was similar to the improvement following administration of lobeline alone. In contrast, combined administration of nicotine and mecamylamine did not result in increased DSDT accuracy. Furthermore, lobeline administration similarly improved accuracy of trials associated with both the light and the tone, while nicotine improved accuracy of trials associated with the light to a much greater degree. These data suggest that the increases in DSDT accuracy associated with lobeline may be expressed through non-nicotinic mechanisms or a nicotinic receptor which is not blocked by mecamylamine.
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  • 178
    ISSN: 1432-2072
    Keywords: Amperozide ; FG5803 ; Haloperidol ; Antipsychotics ; Oral movements ; Chronic administration ; Acute administration ; Acute dystonia ; Tardive dyskinesia ; Extrapyramidal side effects ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Long-term studies of antipsychotic-induced oral movements may serve as a rat model of acute and tardive movement disorders. Vacuous chewing movements (VCM), tongue protrusions (TP), and jaw tremors (TR) were studied in rats during acute and chronic administration of two potential antipsychotics, amperozide and FG5803. Comparisons were made with haloperidol and vehicle. Single intraperitoneal injections of amperozide (0.2, 1, or 5 mg/kg) or FG5803 (1.2, 6, or 30 mg/kg) were without effect on oral behaviors. During long-term drug administration, withdrawal and readministration, endpoint analysis was focused on changes in supranormal oral movements. The maximal mean control frequencies found at 29 sessions during 14 months experiment +2 standard deviations were used to define the upper limit of the normal range. FG5803 (1.2, 6, or 30 mg/kg per day) administered via the drinking water for 12 months, did not produce significant deviations from this normal range with respect to VCM, TP, or TR, and this drug was not studied further. Rats receiving amperozide (0.2, 1, or 5 mg/kg per day) showed dose-related increases in oral movements over the year. The changes began after 3 months of treatment with amperozide 1 and 5 mg/kg per day, but became statistically significant only during the second half of the treatment year. Amperozide 0.2 mg/kg per day did not produce significant changes in oral movements during administration for a year, but drug withdrawal resulted in a significant rise in TP behavior. Haloperidol (1 mg/kg per day) produced increases in supranormal oral movements which tended to level out after 9 months. In all groups with significant elevations (i.e. haloperidol and amperozide 1 and 5 mg/kg per day), there was a persistence of such movements during a month of drug withdrawal. During treatment with amperozide (1 or 5 mg/kg per day), some rats developed a high frequency chewing behavior up to 175 VCMs/min. It is concluded that long-term treatment with amperozide, but not FG5803, produced a tardive pattern of supranormal oral movements. The importance of these findings for the clinical future of amperozide is difficult to predict, due to the unexpected finding of high-frequency chewing, which has not been noticed before during extensive studies of classical neuroleptics.
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  • 179
    ISSN: 1432-2072
    Keywords: 7-OH-DPAT ; Apomorphine ; Dopamine ; D3 receptors ; Locomotor activity ; Progressive-ratio ; Quinpirole ; Rat ; Self-stimulation ; Stereotypies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study assessed the effects of IP injections of (±) 7-hydroxy-2(N,N-di-n-propylamino)tetralin (7-OH-DPAT), a dopamine agonist that has been reported to have preferential affinity for the dopamine D3 subtype of receptor, on four behavioural procedures in the rat: 1) spontaneous locomotion, 2) electrical self-stimulation of the ventral tegmental area (VTA), using the curve-shift procedure 3) operant responding for food under a progressive-ratio (PR) schedule and 4) induction of stereotypies. The effects of (±) 7-OH-DPAT were compared to the effects of apomorphine, a non-specific DA agonist, and quinpirole, a selective D2/D3 agonist. All three dopamine agonists decreased locomotor activity at low doses (0.01–0.3 mg/kg), and only apomorphine had clear locomotor stimulant effects at the highest dose tested (3 mg/kg). The three drugs dose-dependently depressed VTA self-stimulation in a similar way, with low doses inducing a fairly parallel rightward shift of the frequency/rate curves and higher doses flattening the curves. In contrast, responding for food under the PR schedule appeared to be differentially affected by the three agonists: 7-OH-DPAT induced a biphasic effect, with a maximal decrease in lever-pressing at 0.1 mg/kg, followed by a return to baseline levels with increasing doses (0.3–3 mg/kg); quinpirole showed a tendency to decrease responding over the whole dose-range tested with a maximal effect of about 50% of baseline between 0.25 and 1 mg/kg, and apomorphine dose-dependently decreased responding, with rats ceasing to respond at 0.3 mg/kg. All three DA agonists induced stereotypies, but there was a difference in the maximal stereotypy score induced by each of the ligands: 7-OH-DPAT produced a lower maximal effect than quinpirole or apomorphine. This indicates that each of the three dopamine agonists preferentially induced different types of stereotypies. Together, these data suggest that the putative dopamine D3 agonist 7-OH-DPAT, at low doses, has depressant effects similar to those induced by low doses of the other two DA agonists. Differences in the behavioural effects of higher doses were, however, mostly observed in two procedures, PR responding and induction of stereotypies.
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  • 180
    ISSN: 1432-2072
    Keywords: d-Fenfluramine ; Metergoline ; 8-OH-DPAT ; WAY-100635 ; Anorexia ; Satiety sequence ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract These studies investigated the involvement of the 5-HT1A receptor in mediatingd-fenfluramine-induced anorexia in the rat. Non-deprived,d-fenfluramine-treated (3.0 mg/kg) rats consumed a reduced amount of a palatable wet mash and showed a temporal advance in the behavioural sequence consistent with satiety. Thus, rats treated withd-fenfluramine ceased feeding and began resting before corresponding controls. Pretreatment with the selective 5-HT1A receptor antagonist WAY-100635 (1.0 mg/kg) had no effect on either the reduced mash consumption or behavioural satiety sequence ofd-fenfluramine-treated animals at a dose which was found to attenuate the anorexia induced by the 5-HT1A receptor agonist 8-OH-DPAT (0.5 mg/kg). Pretreatment with the nonselective 5-HT antagonist metergoline (1.0 mg/kg) attenuated thed-fenfluramine-induced reduction of mash consumption and the advanced offset of feeding. Metergoline pretreatment had no effect on the advanced onset of resting observed ind-fenfluramine-treated animals. These data suggest thatd-fenfluramine reduces food intake, perhaps by enhancing satiety, via a mechanism which does not involve the 5-HT1A receptor subtype. The implications of these results to the utility of the behavioural satiety sequence as a measure of postprandial satiety are discussed.
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  • 181
    ISSN: 1432-2307
    Keywords: Acinar cell carcinoma ; Fetal pancreas ; Electron microscopy ; Fibrillary inclusion ; Rough endoplasmic reticulum
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report a case of pancreatic acinar cell carcinoma which contained a large number of pleomorphic inclusions with fibrillary internal structures and mature zymogen granules. To clarify the significance of fibrillary inclusions in the differentiation of acinar cells of the pancreas, we further investigated fetal pancreases (gestational weeks 16, 17, 19, 20 and 28). We found two types of inclusions: type A, corresponding to fibrillary inclusion of neoplastic acinar cells, was observed only in a 19-week fetus; type B showed a homogeneous density similar to that of zymogen granules. Type B was observed in all the fetuses after the 17th gestational week. Although the type A inclusion might be generated throught a different mechanism than the type B inclusion, the appearance of a large number of fibrillary inclusions in neoplastic acinar cells may represent a transient form of zymogen granule.
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  • 182
    ISSN: 1432-2307
    Keywords: Alveolar adenoma ; Lung neoplasms ; Flow cytometry ; Electron microscopy ; Proliferating cell nuclear antigen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Alveolar adenoma of the lung is a poorly characterized, uncommon pulmonary lesion with proliferation of alveolar epithelium and septal mesenchyme. We describe the electron microscopy, immunohistochemistry and DNA flow cytometry in a case of alveolar adenoma in a 55-year-old woman. Alveolar adenoma appears to be a distinct benign neoplasm of the alveolar structures. Our findings further suggest that it is not a precursor of bronchioloalveolar carcinoma or other type II pneumocyte lesions of presumed malignant potential.
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  • 183
    ISSN: 1432-0878
    Keywords: Key words: Growth factors ; Brain-derived neurotrophic factor ; Immediate-early genes ; Tyrosine hydroxylase ; Glia ; Cell culture ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Glial cell line-derived neurotrophic factor (GDNF) is a highly selective neurotrophic factor for midbrain dopaminergic neurons and might thus be of potential use in the therapy of Parkinson’s disease. In this study, we present evidence that the survival-promoting action of GDNF on dopaminergic neurons requires the concurrent activation of cAMP-dependent signaling pathways. In serum-free low density cultures of the dissociated embryonic day 15 mesencephalon, dopaminergic neurons undergo constant cell death as evidenced by a 90% reduction in tyrosine hydroxylase-immunoreactive (TH-IR) cell numbers between days 1 and 9 of cultivation. This decline was not affected by GDNF (5 ng/ml) within the initial 3 days of cultivation, but was in part attenuated with prolonged treatment. In contrast, stimulation of 3-day-old mesencephalic cultures with GDNF induced c-fos expression in 73% of all TH-IR neurons, indicative for the early presence of efficient signal-transduction coupling in these neurons. Combined treatment of mesencephalic cultures with dibutyryl cyclic AMP (dbcAMP; 100 μM) and GDNF accelerated the onset of the survival effects of GDNF on dopaminergic neurons, resulting in a 1.5-fold increase in the number of surviving TH-IR neurons at 3 days in vitro. In addition, activation of cAMP-dependent signal pathways significantly potentiated the survival-promoting effects of GDNF on dopaminergic neurons in older cultures. dbcAMP alone had no effect on dopaminergic cell survival. Taken together, our findings suggest that the action of GDNF on midbrain dopaminergic neurons is modulated by other extracellular signals.
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  • 184
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    Cell & tissue research 286 (1996), S. 249-255 
    ISSN: 1432-0878
    Keywords: Key words: GDNF ; NT-4/5 ; Tachykinin ; Dopamine ; Amphetamine ; PPT-A ; Survival ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Glial-cell-line-derived neurotrophic factor (GDNF) is a novel trophic factor with potent trophic effects on several neuron populations in the central and peripheral nervous system. In the present study, we have investigated and compared the potential of dopamine and metamphetamine with that of the two striatal neurotrophic factors, viz., GDNF and neurotrophin-(NT)-4/5, to regulate substance P and its preprotachykinin-A mRNA in organotypic striatal slices from postnatal (day 10) rats. Incubation for 2 weeks with 10 ng/ml GDNF significantly increased substance-P-like immunoreactivity determined by radioimmunoassay. Similarly, the corresponding preprotachykinin-A mRNA increased after 1 and 2 weeks of incubation, as analyzed by in situ hybridization. NT-4/5 exhibited similar effects.The dopamine-releasing agent metamphetamine stimulated substance-P-containing neurons in 1-week-old striatal slices, whereas dopamine stimulated substance-P-like immunoreactivity in 1- and 2-week old striatal cultures. The effects of dopamine and GDNF were not additive. We conclude that substance-P-containing medium-sized spiny neurons in the striatum are under both dopaminergic and growth factor control by GDNF and NT-4/5, which are both synthesized in the striatum. This adds a previously unknown role to those that have been established for GDNF in the nigrostriatal system.
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  • 185
    ISSN: 1432-0878
    Keywords: Key words: Electrocyte ; Intermediate filaments ; Desmin ; Cytoskeleton ; Electron microscopy ; Electrophorus electricus (Teleostei)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Desmin protein is an abundant constituent of the intermediate filaments in the electrocytes of the electric organ of the electric eel Electrophorus electricus. Polyclonal antibodies were raised against purified desmin from the electric organ and used for immunolabeling of the protein in reconstituted filaments. In thick sections of the main electric organ that has been stained with fluorescein-labeled desmin-specific antibodies, light microscope revealed a diffuse meshwork of desmin filaments dispersed in the cytoplasm of electrocytes. In the region under the membrane, the immunostaining was slightly more intense than elsewhere. The meshwork of intermediate filaments composed of desmin was examined by electron microscopy of the main electric organ. Immuno-gold labeling demonstrated a widespread meshwork of desmin filaments in the cytoplasm and in close association with the plasma membrane. These observations suggest that intermediate filaments play a role in the maintenance of the morphology of electrocytes and, as an intracellular meshwork spanning the width of the cell, they may contribute to the organization of the intracellular compartments.
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  • 186
    ISSN: 1432-0878
    Keywords: Key words: Innervation ; Heart ; Intracardiac neurone ; Nitric oxide ; Immunocytochemistry ; Electron microscopy ; Rat (Sprague Dawley) ; Guinea-pig (Dunkin Hartley)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. The nitric oxide synthase-immunoreactivity and NADPH-diaphorase activity of intracardiac neurones in the rat and guinea-pig was studied at the ultrastructural level. While some nitric oxide synthase-containing intracardiac neurones were very heavily labelled, with electron-dense immunoprecipitate distributed throughout the neuronal cell bodies and their processes, most of the labelled neurones exhibited a lighter and more patchy distribution of nitric oxide synthase-immunoreactive material. Synapses made by nitric oxide synthase-negative nerve fibres with labelled intracardiac neurones were seen. Conversely, many nitric oxide synthase-containing nerve fibres that made synaptic contacts with unlabelled intracardiac neurones were also observed. Some small granule-containing cells were nitric oxide synthase-immunoreactive and were associated with unlabelled nerve terminals, while non-immunoreactive small granule-containing cells that were innervated by nitric oxide synthase-immunoreactive nerves were also seen. Small patches of osmiophilic electron-dense material were observed in the cytoplasm of NADPH-diaphorase-positive intracardiac neurones. This is the first description of the ultrastructural distribution of nitric oxide synthase-immunoreactivity and NADPH-diaphorase activity in a subpopulation of intracardiac neurones of rat and guinea-pig heart and provides further evidence in support of a role for nitric oxide in the local control of the heart by intrinsic neurones.
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  • 187
    ISSN: 1432-0878
    Keywords: Key words: Ocellus ; Photoreceptor cells ; Retinal degeneration ; Subrhabdomeric cisternae ; Electron microscopy ; Immuno-electron microscopy ; Phosphatidylinositol transfer protein ; Drosophila melanogaster (Insecta)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. We studied the structure of ocellar photoreceptor cells of Drosophila melanogaster, particularly the subrhabdomeric cisternae which our previous studies have shown to be essential structures for turnover of photoreceptive membranes in compound eyes. Each ocellus contained elongated photoreceptor cells with rhabdomeres positioned distally. In the subrhabdomeric regions, endocytotic invaginations were frequently observed, suggesting active turnover of photoreceptive membranes. In the vicinity of the photoreceptive microvilli, membranous structures similar to the subrhabdomeric cisternae in compound eyes were observed. These membranous structures were immunopositive for the rdgB protein, a phosphatidylinositol transfer protein that is localized to the subrhabdomeric cisternae in compound eyes. The ocellar photoreceptor cells of the retinal degeneration mutants (rdgA,B) were also studied. In these mutants, retinal degeneration has been reported to start, in compound eyes, with the disappearance of the subrhabdomeric cisternae. We found that the ocellar subrhabdomeric cisternae also disappear during the initial stage of retinal degeneration. From these observations, we conclude that the mechanism of photoreceptive membrane turnover in ocellar photoreceptor cells involves the rdgB and probably the rdgA proteins which are associated with subrhabdomeric cisternae, as is the case for photoreceptive membrane turnover in compound eyes.
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  • 188
    ISSN: 1432-0878
    Keywords: Key words: Mineralization ; Matrix vesicles ; Dentine ; Ultrastructure ; Element analysis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. The purpose of this study was to elucidate the mineralization process of mantle dentine by ultrastructural and element-analytical investigation of matrix vesicles and successive stages. Upper second molars of albino rats were cryofixed and embedded in resin after freeze drying. Semithin dry sections were prepared for analyzing the calcium and phosphorus concentrations in the mineralized matrix vesicles or noduli, larger mineralized islands, and the mantle dentine. For ultrastructural studies, it was necessary to reduce section contact with hydrous fluids to a minimum in order to avoid preparation artifacts. The first mineral deposits were recognized as dot-like formations both in the interior of matrix vesicles and in association with the inner vesicle membrane. This indicated the existence of mineral nucleating sites located both at the inner membrane and at calcium-phosphate-binding macromolecules in the interior of the matrix vesicles. A significantly higher mineral content was found in mineralized matrix vesicles than in the mineralized extravesicular regions of the mineralized islands, suggesting the existence of a rapidly and densely mineralizing matrix in the matrix vesicles. A significant increase in mineral content per volume proceeding from the mineralized islands to mantle dentine suggested a further increase in the density of mineral.
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  • 189
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    Cell & tissue research 284 (1996), S. 125-142 
    ISSN: 1432-0878
    Keywords: Key words: Chordotonal organ ; Scolopidium ; Mechanoreceptor ; Sensilla ; Electron microscopy ; Phylogenesis ; Teleogryllus commodus (Insecta)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. More than 50 chordotonal sensilla, or scolopidia, embedded entirely in the integument were found in each side of the genital chamber wall in the female cricket, Teleogryllus commodus. Their cell bodies lie among the epidermal cells, and the tips of their dendrites terminate in the cuticle. About half of them contain two sensory cells (two-cell scolopidium), the others only one (one-cell scolopidium). The sensory cell in the one-cell scolopidium is the type-1 cell. In the two-cell scolopidium one is type-1 and the other type-2. Regardless of the number of sensory cells, they are all amphinematic. In the two-cell scolopidium only the type-2 dendrite, rich in microtubules, penetrates into the cuticle, bifurcates and terminates in the tube enclosed by an attachment cell; the type-1 never extends into the cuticle. On the other hand, the type-1 cell in the one-cell scolopidium projects its apex into the cuticle. The unique topography and structure of these scolopidia lead to the following hypothesis about the phylogenetic relationship between the scolopidia and other kinds of sensilla: the type-1 scolopidial sensory cell buried in the integument may be the original model, which through the loss of the long regular axoneme has given rise to type-2 cells. Modification of the apical region, the tubular body or ramification, may have lead to the cuticular sensilla corresponding to the development of the cuticular apparatus, and the scolopidia may have been withdrawn into the body cavity to form ordinary chordotonal organs.
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  • 190
    ISSN: 1615-6102
    Keywords: Aging ; Alzheimer's disease ; Brain ; Cell-free system ; Membranes ; Membrane trafficking ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary A cell-free transfer system was used to measure capacity of brain membranes to support membrane renewal. To study transfer in brain, radiolabeled donor microsome fractions were prepared using brain slices from rats or frozen human brain autopsy specimens. Acceptor fractions, prepared from fresh or frozen rat brain or frozen human brain autopsy specimens, were immobilized on nitrocellulose. The complete reconstituted transfer system contained ATP plus ATP-regenerating system (or NADH) as a source of energy and brain cytosol. Slices of frozen brain incorporated acetate into membrane lipids with approximately the same efficiency as fresh brains. This efficiency declined with storage at 4 °C but only slowly. Donor fractions labeled with acetate from frozen slices exhibited specific transfer (37 °C minus 4 °C) of labeled membrane lipids with efficiencies comparable to fresh. The acceptor fraction could be prepared either from fresh or frozen material. Transfer was on the average two-fold stimulated by ATP at 37 °C compared to no ATP. Transfer also was stimulated by NADH. Analysis of linear transfer rates between 0 and 30 min revealed no significant effect of delay time or of time of prolonged storage on transfer efficiency beyond an initial decline of ca. 25% observed within the first two weeks after freezing. A decline of transfer was obtained with brains as the animals aged.
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  • 191
    ISSN: 1619-7089
    Keywords: Pinhole collimator ; Single-photon emission tomography ; High resolution ; Myocardial infarction ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purpose of this study was to evaluate the accuracy of myocardial imaging by means of high-resolution single-photon emission tomography (SPET) with a pinhole collimator in rats with experimental infarction. Myocardial infarctions were induced in male Wistar rats by ligation of the left coronary artery for 30 min, followed by reperfusion. Two days after the reperfusion, pinhole SPET was performed after the intravenous administration of 111 MBq of thallium-201 chloride, using a rotating gamma camera equipped with a pinhole insert (2.0-mm aperture) in a low-energy pinhole collimator. SPET projection data were collected at 6° increments over 360° using a 4-cm radius of rotation to reconstruct the short- and long-axis images. Projection data were acquired in 15 or 30 s, the SPET imaging being accomplished within 40 min after the injection of201T1. After SPET, the rats were sacrificed to remove the hearts for autoradiography (ARG) and nitroblue tetrazolium (NBT) staining as a visual correlative study. Quantitative correlative studies between pinhole SPET and ARG were performed with linear regression analysis for infarct size and distribution properties (relative counts on SPET images and relative density on autoradiographs) on the short-axis sections. All infarcts (4 mm in minimum diameter) in seven rats were detected by pinhole SPET. The SPET images in rats with or without myocardial infarction were consistent with the findings of ARG and NBT staining. There were significant correlations between pinhole SPET and ARG with respect to the infarct size (r=0.933,P 〈0.001;n=15) and the relative radiotracer distribution (r=0.931,P 〈0.001; n=68). This study therefore confirmed the accuracy of myocardial pinhole SPET imaging in rats with myocardial infarction. This method may partially substitute for ARG and prove useful for assessing new myocardial imaging agents in vivo in small laboratory animals.
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  • 192
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    European journal of applied physiology 73 (1996), S. 130-135 
    ISSN: 1439-6327
    Keywords: Experimental auto-immune encephalomyelitis ; T-Cells ; Rat ; Auto-immunity ; Exercise
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of the study was to determine whether different programmes of exercise influence adoptive monophasic experimental auto-immune encephalomyelitis (adoptive EAE), a paralytic disease mediated by T-cells. Adoptive EAE was induced by the transfer of activated encephalitogenic T-lymphocytes into syngeneic recipients (Lewis rats, n = 85) and its development was followed by two independent observers. The results showed that 2 days of severe exercise (250 and 300 min) performed after the adoptive transfer of EAE slightly delayed the onset of the disease (P 〈 0.008) and the day of its maximal severity (P 〈 0.016) without affecting the overall severity of the disease. When this programme of exercise was performed before the cell transfer, it had no effect (P 〉 0.05). Two more moderate exercise programmes (5 × 120 min of running at constant speed or 5 × 60 min of running at variable speed, 5 consecutive days) performed between the adoptive transfer and the onset of the disease did not modify the development of the clinical signs of adoptive EAE (P 〉0.05). These results showed that severe exercise slightly influenced the effector phase of monophasic EAE and confirmed that physical exercise performed before the onset of experimental auto-immune diseases did not exacerbate the clinical signs.
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  • 193
    ISSN: 1439-6327
    Keywords: Short-term dietary change ; Glycogen Triacylglycerol ; Lipolysis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of short-term diet change from high fat (F) to high carbohydrate (C) (or vice versa) on the storage and utilization of glycogen and triacylglycerol (TG) in muscle and liver were studied in untrained rats. Rats were fed on an F or C diet for 28 days. For an additional 3 days, half of the rats in both F and C groups were fed the same diets as before (F-F and C-C) and the other half of the rats were switched to the counterpart diets (F-C and C-F). On the final day of the experiment, half of the rats in each diet group were exercised by swimming for 1.5 h and the other half were rested. Short-term diet change from F to C diets increased, but the change from C to F diets decreased, glycogen stores of soleus and plantaris muscles and liver, resulting in no difference in glycogen stores between F-C and C-C, and between F-F and C-F. The dietary change also had an affect on TG stores of red gastrocnemius muscle and liver - however, muscle TG stores were still higher in F-C than in C-C and C-F, and there were no differences in liver TG stores between F-C and C-F. Exercise decreased muscle glycogen contents markedly in F-C and C-C, whereas, it decreased muscle TG concentrations in F-F and C-F. Liver glycogen depletion was lower in F-C than in other groups. Lipolytic activities of epididymal adipose tissue at rest and postexercise were no differences between F-F and F-C, and were higher in F-C than in C-C and C-F. β-adrenergic receptor binding was determined with [125I] iodocyanopindolol, and maximal numbers of β-adrenergic receptor of plasma membrane from perirenal adipose tissue were approximately 170%–200% higher in F-C than in other groups at rest and postexercise. These results suggested that short-term C diet fed rats adapted to F diet enhanced not only glycogen stores of muscle and liver but also did not decrease lipolytic activity of adipose tissue with increased β-adrenergic receptor density, resulting in the preservation of energy reserves (glycogen and TG) of muscle at rest, and liver glycogen sparing during exercise.
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  • 194
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    European journal of applied physiology 72 (1996), S. 496-501 
    ISSN: 1439-6327
    Keywords: Hyperthyroidism ; Glycogen ; Skeletal muscles ; Exercise ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of the present study was to examine the rate of glycogen mobilization during exercise and the rate of the postexercise glycogen replenishment in different muscle types [white (WG), and red (RG) gastrocnemius, soleus (S) and diaphragm (D)] in rats treated with triiodothyronine (T3, group T). Rats of the control group (C) were treated with saline. The animals were made to run on a treadmill set at 0° gradient and at a speed of 1200 m·h−1. The time taken to reach exhaustion in group C was 188 (SD 23) min, whereas in group T, it was only 63 (SD 12) min. The content of glycogen in all muscles of the rats from group T at rest and during exercise was significantly lower than in group C at each corresponding time. At exhaustion, the glycogen content was in WG(C) 34.79 (SD 4.65), (T) 20.10 (SD 4.10); in RG(C) 22.82 (SD 4.66), (T) 16.50 (SD 2.00); in S(C) 14.85 (SD 2.48), (T) 11.90 (SD 2.93); in D(C) 18.18 (SD 3.49), (T) 7.54 (SD 3.36) (μmol of glucosyl units·g−1). The amount of glycogen mobilized during exhausting exercise in RG, S and D was similar in both groups whereas in WG it was much higher in rats of group T than in group C. The concentration of glycogen returned to pre-exercise values in each muscle 3 h after exercise. The net amount of glycogen resynthetized during 3 h of recovery depended on the muscle type. It was in WG(C) 3.30, (T) 18.03; in RG(C) 21.34, (T) 25.88, in S(C) 34.00, (T) 17.68, and in D(C) 17.25, (T) 12.22 μmol of glucosyl units·g−1 (each number represents the difference between the means). It concluded that treatment with T3 markedly affects this exercise-induced metabolism of glycogen in each muscle type. From our study it is suggested that low muscle glycogen content may contribute to a reduction in exercise performance in hyperthyroidism.
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  • 195
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    International urogynecology journal 7 (1996), S. 30-36 
    ISSN: 1433-3023
    Keywords: Aging ; Incontinence ; Rat ; Smooth ; Sphincter ; Striated ; Urethra
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Muscles in the limbs change with age, but the aging process of urethral muscles is unknown. Therefore, we compared smooth and striated muscle content in the female rat urethra in young (12 month) and old (32 month) animals, using immunochemical techniques. All the striated skeletal fibers at both ages contain slow myosin. Urethral diameter does not change with age (young, 1.44±0.08 mm; old, 1.46±0.10 mm,n=5), nor does the external sphincter width (young, 0.088±0.016 mm; old, 0.080±0.017 mm,n=5). Neither smooth nor skeletal muscle volume in the urethra is changed with age (skeletal: young, 20.72±2.94%; old, 19.95±2.35%. Smooth: young, 22.26±2.98%; old, 26.75±2.35%,n=5). The external striated sphincter is separate and distinct from the pubococcygeal region of the levator ani muscle, but is closely apposed to another layer of longitudinally oriented fibers into the vaginal musculature. The morphometric analysis shows no difference in urethral architecture in aging female rats.
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  • 196
    ISSN: 1438-8359
    Keywords: Cervical sympathectomy ; Gonadotropin-releasing hormone ; Hypothalamus ; Median eminence ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To examine the effects of cervical sympathectomy on the transport of gonadotropin-releasing hormone (GnRH) between the hypothalamic neurons and the median eminence, 16 male rats were assigned into four groups: control (C), light (L), light-sympathectomy (LS), and light-colchicine (LC). The C group was kept under a normal circadian rhythm for 2 weeks, and the L group was kept under continuous exposure to light for the same period. The LS group underwent bilateral cervical sympathectomy before being kept under continuous light conditions for 2 weeks. The LC group received colchicine into the cerebral ventricle after being kept under continuous light for 12 days; subsequently, this group was also housed for 2 days under continous light. After these procedures, blood was collected and serum luteinizing hormone (LH) levels were measured. All rats were perfused with a fixative, and GnRH neurons around the anterior commissure, as well as GnRH fibers and granules in the median eminence, were stained immunohistochemically. The L group showed a decreased number of GnRH neurons, increased concentrations of GnRH fibers and granules, and an increased LH level; however, in the LS and LC groups, these changes were not seen. The response in the LS group resembled that in the LC group. Considering the action of colchicine, which inhibits axonal transport, it is suggested that cervical sympathectomy also inhibits axonal transports of GnRH between the GnRH neurons and the median eminence during continuous exposure to light.
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  • 197
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    Methods in cell science 18 (1996), S. 15-18 
    ISSN: 1573-0603
    Keywords: Angiogenesis ; Endothelial cells ; Angiogenesis analysis ; Electron microscopy ; Cell culture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Determination of the structural characteristics of angiogenesis requires a procedure protective of the forming vascular fibers and the endothelial cell monolayer exhibiting cord formation. This report describes in situ fixation of angiogenic cultures in 96-well plates and the subsequent double embedding processing for electron microscopy. Cross sections of the monolayer are obtained without damage of the incipient capillaries.
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  • 198
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    European archives of oto-rhino-laryngology and head & neck 253 (1996), S. 205-213 
    ISSN: 1434-4726
    Keywords: Nasal neuropeptides ; Perennial rhinitis ; Mucosal glands ; Immunofluorescence ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to study morphological effects on the nasal and sinus mucosa, New Zealand White rabbits underwent either unselective, regional sectioning of sensory and parasympathetic nerve branches or topical treatment of the mucosa with capsaicin. Ten days after treatment, mucosal specimens were analyzed by light and electron microscopy. Immunohistochemistry was used to evaluate neuropeptides present, in particular substance P, calcitonin gene-related peptide, vasoactive intestinal peptide and neuropeptide Y. In surgically denervated rabbits, mucosal glands were found to be enlarged and contained an increased number of zymogen granules having a bipartite substructure. Topical capsaicin application caused localized epithelial changes in the sinus mucosa and maxilloturbinal region of the nose, including clotting of cilia and an increased number of goblet cells. Reduced amounts of all neuropeptides investigated were found in the surgically denervated animals, while topical capsaicin treatment had only marginal effects on the mucosal neuropeptide content. The morphological changes observed after surgical denervation suggest an imbalance between neural stimulation and secretory capacity of the mucosal glands. These findings could explain the difference in clinical effect noted between sectioning of the vidian nerve and topical treatment with capsaicin in patients with perennial rhinitis.
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  • 199
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    European archives of oto-rhino-laryngology and head & neck 253 (1996), S. 214-221 
    ISSN: 1434-4726
    Keywords: Formalin fixation ; Mucous cell ; Submandibular gland ; Morphology ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The features of mucous cells in 10% formalin (FA)-fixed submandibular glands differ markedly from those fixed in glutaraldehyde (GA). We therefore studied morphological changes in mucous cells during 10% FA fixation. Mucous cells were fixed in either 10% FA, neutral sodium-phosphate-buffered (Na-PBed) 10% FA, ice-cold 10% FA or an ice-cold fixative mixture of 2.0% paraformaldehyde (PA) and 0.5% GA. Two different methods were used: immersion fixation and venous perfusion fixation. The 10% FA-fixed tissues had elliptical or flattened nuclei, a clear cytoplasm and no secretory granules. Tissues fixed with the fixative mixture displayed almost round nuclei, a broad endoplasmic reticulum and abundant secretory granules in the cytoplasm. Tissues immersion-fixed with neutral Na-PBed 10% FA or perfusion-fixed with ice-cold 10% FA had almost the same light microscopic appearance as that of the mixture-fixed tissues. To elucidate the process of morphological changes during 10% FA fixation at room temperature, samples immersed in 10% FA for varying periods of time were postfixed immediately in the fixative mixture and exposed to microwave irradiation. This method produced a variety of findings, even within the same section. There was a significant difference in the findings seen in the center of the section and at the periphery. The initial changes caused by 10% FA were rupture of the secretory granules located in the perinuclear region and destruction of the perinuclear organelles such as Golgi apparatus, mitochondria and endoplasmic reticulum. Absorption of the endoplasmic reticulum progressed so that the pennuclear region became translucent. To obtain a better structure in mucous cells from the fixed submandibular gland tissues, an appropriate fixative such as GA should be used and the fixative should infiltrate into the tissue as quickly as possible.
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  • 200
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    European archives of oto-rhino-laryngology and head & neck 253 (1996), S. 142-146 
    ISSN: 1434-4726
    Keywords: Immunocompetent cells ; Mucosal immune system ; Larynx ; Immunohistology ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The larynx can be divided into a supraglottic, a glottic and a subglottic area, each serving different functions. In many cases of laryngitis the site of infection is located in one area, leaving other areas unaffected. It seems reasonable to speculate that the underlying cause of the heterogeneous infection pattern in the larynx is the different processing of infectious agents. Therefore, the number and distribution of granulocytes, macrophages, dendritic cells, natural killer cells and T and B lymphocytes in the normal laryngeal mucosa of young rats were studied. The results show that, with the exception of granulocytes, all subpopulations were present in different numbers. Many macrophages and dendritic cells but only a few natural killer cells and T and B lymphocytes were located in the mucosa. Dendritic cells, natural killer cells and T and B lymphocytes were rarely present in the vocal fold area, whereas in the subglottic area they were present in high numbers. Thus, differences in the composition of immunocompetent cell populations between laryngeal areas were detectable.
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