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  • 1
    ISSN: 1432-0428
    Keywords: Somatostatin ; diabetic Chinese hamsters ; islet cells ; A1-cells ; glucagon ; insulin ; hypothalamus ; stomach
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The inhibitory effects of somatostatin on the release of insulin and glucagon, as well as its localization to the A1-cells (D-cells) of the pancreatic islets, suggest a role of this peptide in carbohydrate metabolism. In the present study we have measured the percentage islet volume, the total weight of the A1-cells and the somatostatin concentration in the pancreas of normal and spontaneously diabetic Chinese hamsters. In addition, the concentration of somatostatin in the stomach and hypothalamus as well as the insulin and glucagon content of the pancreas were evaluated. The percentage islet volume in the normal hamsters was 0.66±0.12, which was in marked excess of that in the diabetic group, 0.38±0.04. Similarly, the total weight of the A1-cells in the controls, 0.17±0.02 mg, was significantly larger than that in the diabetic animals, 0.12±0.02 mg. In agreement with these findings there was also a decreased pancreatic concentration of insulin and somatostatin, whereas the glucagon concentration was in the normal range. Also the stomach of the diabetic hamsters showed a decreased concentration of somatostatin. In the hypothalamus the total content of somatostatin appeared similar in the two groups of animals, but when expressed per mg wet weight this value was also decreased in the diabetic hamsters. These observations strongly suggest that, in the diabetic Chinese hamster, apart from the well-known B-cell deficiency there exists also a decreased functional activity of the somatostatin-producing cells.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 14 (1978), S. 1-13 
    ISSN: 1432-0428
    Keywords: Somatostatin ; hypothalamus ; hypophysis ; growth hormone ; insulin secretion ; neurotransmitters
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1106
    Keywords: Axotomy ; Retrograde tracing ; Spinal cord ; Motoneurons ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The content of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) in motoneurons was studied in four motor pools supplying muscles in the rat hind limb subserving different types of motor activity. The motor pools were identified by retrograde labeling with horseradish peroxidase or fluorophore-conjugated dextran amines, which were injected into the soleus, tibialis anterior, lateral gastrocnemius, or abductor digiti minimi muscles. After processing for immunohistochemistry, a semiquantitative evaluation was carried out to estimate the proportion of strongly, intermediately, and weakly labeled motoneurons, as well as motoneurons totally lacking CGRP staining. This revealed a considerable diversity in the intensity of CGRP labeling even for motoneurons in the same motoneuron pool. Thus, strongly labeled cells, as well as cells devoid of CGRP label, were found in all four motoneuron pools. However, a difference was found in the distribution of motoneurons innervating muscles with a dominant composition of fast and slow motor units, respectively, in that a larger fraction of the latter type lacked CGRP-LI. Moreover, generally motoneurons in the small motor units of the abductor digiti minimi muscle displayed weaker staining, and a larger proportion of cells was totally devoid of CGRP-LI (16%) compared with larger motor units of the other three muscles (1–10%). Small-sized cells within the γ-motoneuron size range were weakly stained or, more frequently, totally devoid of CGRP label (50%) as compared to larger cells, presumably representing α-motoneurons (1–16%). Five days after axotomy all four studied motoneuron pools displayed stronger CGRP labeling than corresponding unlesioned pools. However, a considerable variation in CGRP labeling persisted also among axotomized motoneurons. These results indicate that motoneurons normally display a great variation in CGRP-LI levels, but that motoneurons of small and slow-twitch motor units in general have lower levels than motoneurons of large and fast-twitch motor units, respectively. After axotomy, CGRP-LI increases in lesioned motoneuron pools compared with normal, but in a fraction of the axotomized motoneurons the increase seems to be discrete or even absent. The possible physiological implications of these findings are discussed.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1106
    Keywords: Key words Aspartate ; Cochlea ; Glutamate ; Hearing ; Immunoreactivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We have used the perfused guinea-pig temporal-bone preparation to study the sound-evoked efflux of aspartate and glutamate, which are putative afferent transmitters in the cochlea. The cochlea was stimulated with white noise at 89, 95, and 101 dB SPL. Cochlear function was monitored by recording the endocochlear potential, the cochlear microphonic, and the summating potential. In silence, there was a low basal efflux of both amino acids. A significant and intensity dependent sound-evoked efflux of aspartate was observed at all levels, whereas a significant efflux of glutamate was found only at the 101 dB SPL level. Immunohistochemistry of sections from the organ of corti showed an ubiquitous distribution of glutamate-like immunoreactivity in the sensory organ and ganglion, whereas aspartate-like immunoreactivity was found in the region of the inner hair cells and in the spiral ganglion. In view of these findings, we suggest that not only glutamate, but also aspartate may have a neurotransmitter role in the afferent pathway of the cochlea.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1106
    Keywords: Ibotenic acid ; Kainic acid ; Neurotoxins ; Neuronal degeneration ; Striatum
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Possible neurotoxic actions of intracerebral injections of ibotenic acid, a conformationally restricted analogue of glutamic acid, have been evaluated in rat brain and compared with those of kainic acid. Light microscopical analysis revealed that ibotenic acid produced a marked disappearance of nerve cells in all areas studied, namely striatum, the hippocampal formation, substantia nigra and piriform cortex. Lesions in areas distant to the injection site were not seen. Axons of passage and nerve terminals of extrinsic origin did not seem to be damaged, since, e.g., no apparent degeneration of the dopaminergic terminals in the neostriatum was observed except for a small area surrounding the cannula. In the neostriatum, enkephalin immunoreactive neuronal cell bodies as well as nerve terminals disappeared after injection of ibotenic acid into this nucleus. After injection into the substantia nigra tyrosine hydroxylase immunoreactive cell bodies in the zona compacta disappeared, whereas no certain effect could be seen on the enkephalin immunoreactive nerve fibers. In vitro experiments, conducted with striatal synaptosomal and membrane preparations, showed that ibotenic acid differed from kainic acid by being devoid of a significant inhibitory effect on high affinity glutamate uptake and by having a low affinity for 3H-kainic acid binding sites. Furthermore, ibotenic acid did not interfere with the binding of a number of radioligands for other transmitter receptors. As compared to kainic acid, ibotenic acid has the advantage of being less toxic to the animals and of producing more discrete lesions, possibly due to faster metabolism and/or other fundamental biochemical differences. Because of these special features, ibotenic acid seems to represent a valuable new tool in the morphological and functional analysis of central neuronal systems.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1106
    Keywords: Basal ganglia ; Transmitters ; Neuropeptides ; GABA ; Enkephalin ; Striato-nigral pathways
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of striatal ibotenic acid lesions on dynorphin-, substance P- and enkephalin-like immunoreactivities in the substantia nigra has been studied with immunohistochemistry as well as biochemistry. A comparison was made with the effects produced by intranigral ibotenic acid lesion and by 6-hydroxy-dopamine injection into the medial forebrain bundle. In addition, the effect of the striatal lesions on nigral glutamic acid decarboxylase (GAD)-positive structures was analysed with immunohistochemistry. The effect of the lesions was analysed functionally in the Ungerstedt rotational model, in order to obtain a preliminary evaluation of the extent of the lesions. The striatal lesions produced a parallel depletion of dynorphin and substance P levels in the substantia nigra, pars reticulata, ipsilateral to the treated side, which was dependent upon the extent and location of the lesion. Ibotenic acid lesions into the tail and the corpus of the striatum produced stronger nigral-peptide depletion than lesions in the head and the corpus of the striatum. Comparison of placement of lesions and localization of depleted area in the substantia nigra revealed a topographical relationship. Furthermore, the nigral depletion patterns of dynorphin and substance P were similar. The immunohistochemical analysis revealed that also GAD-positive fibers in the pars reticulata to a large extent disappeared after striatal lesions, in parallel to the dynorphin- and substance P-positive fibers. However, the depletion was less pronounced for GAD than for the peptides, probably related to presence of local GABA neurons in the zona reticulata of the substantia nigra. These results indicate that with the types of lesion used in this study it is not possible to provide evidence for a differential localization within the striatum of dynorphin-, substance P- and GABA-positive cell bodies projecting to the substantia nigra. The radioimmunoassay showed that (Leu)- but not (Met)-enkephalin was affected to the same extent as the dynorphin peptides, supporting the view that (Leu)-enkephalin in the pars reticulata of the substantia nigra is derived from proenkephalin B and not from proenkephalin A. In the immunohistochemical analysis (Met)-enkephalin-like immunoreactivity could only be detected in the pars compacta of the substantia nigra and did not seem to be affected by any of the lesions. The striatal lesions produced a behavioural asymmetry, which could be disclosed by stimulating the rats with apomorphine, which produced ipsilateral rotation. The total number and intensity of the rotation were closely correlated to the extent and location of the striatal lesion as well as to the amount of dynorphin and substance P depletion found in the substantia nigra of the treated side. The results provide further evidence for the presence of a dynorphin-containing system with fibers originating mainly in the corpus and tail of the striatum and terminating in the zona reticulata of the substantia nigra and may, similarly to the previously characterized substance P and GABA containing pathways, have a role in the control of motor behaviour.
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  • 7
    ISSN: 1432-1106
    Keywords: Transplantation ; Medullary and mesencephalic raphé ; Host spinal cord ; Transmitter phenotypy ; Fibre outgrowth ; Selective neuronal death
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Suspensions of cells derived from the mesencephalic raphé or medullary raphé regions of the 13–14 day old embryonic rat brain were injected into the spinal cord of adult rats which had been previously denervated with 5,7-dihydroxytryptamine. At periods of up to 12 months after grafting, the spinal cords were taken for immunohistochemical analysis of 5-hydroxytryptamine (5HT), substance P (SP) and thyrotropin releasing hormone (TRH). In nearly all cases, surviving transplants were found. The grafts derived from mesencephalic raphé cells contained neurones which were immunoreactive to 5HT, or SP, but not both together. On average 4% of the total possible number of the available embryonic mesencephalic serotoninergic cells were found. A very dense outgrowth of 5HT positive fibres from the transplant was observed, extending up to 1.5 cm in both the caudal and rostral directions from the graft locus. Some SP immunoreactive fibres were also apparent near the implant. The grafts derived from the medullary transplant also contained 5HT-immunoreactive cells, comprising on average 25% of the total 5HT neurones available from the embryonic medullary primordium. In addition, neurones colocalizing 5HT together with SP and TRH were visible, closely reflecting the situation found in the medullary raphé in situ. Dense plexi of fibres containing 5HT-LI extended both caudally and rostrally up to 12–15 mm from the transplant. Outgrowth of SP and TRH varicose fibres was also demonstrable, although to a lesser degree than for 5HT. It was also possible to find many motoneurones surrounded by varicose fibres containing both 5HT and SP, in contrast to the situation with the mesencephalic grafts, where no such patterns of innervation were seen. The experiments indicate that the milieu of the spinal cord may compromise the survival of mesencephalic raphé 5HT neurones far more than of medullary serotonin cells. However, despite this effect on cell survival, the outgrowth of fibres from the remaining mesencephalic 5HT neurones was apparently unaffected by their ectopic position. Similarly, the transmitter content of both classes of raphé cells was largely unaltered, either by the transplantation process or by the environment into which they were placed. It is concluded that although the adult denervated spinal cord can selectively affect neuronal survival, it is incapable either of inducing in other serotoninergic cells placed within it the transmitter phenotype typical of medullary raphé neurones, or of causing those ectopically located 5HT cells to form connections appropriate to the descending serotonin fibres.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 38 (1980), S. 1-10 
    ISSN: 1432-1106
    Keywords: TRH-like immunoreactivity ; PAP technique ; Electron microscopy ; Neuronal localization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary With the peroxidase-antiperoxidase (PAP) method TRH-like immunoreactivity (TRH-LI) was observed in certain neurons of the central nervous system. Their distribution agreed well with findings previously obtained with the indirect immunofluorescence technique. At the ultrastructural level electron-dense precipitates representing TRH-LI were observed in so-called large dense core vesicles, which were localized both in the cytoplasm of some hypothalamic neuronal cell bodies, as well as in boutons in the hypothalamus and spinal cord. The boutons often seemed to form axo-somatic or axodendritic synapses.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-1106
    Keywords: 5-Hydroxytryptamine ; Substance P ; Thyrotropin releasing hormone ; Transplantation ; Medullary and mesencephalic raphé ; Fibre outgrowth ; Selective neuronal death
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Suspensions of cells taken from the mesencephalic or medullary raphé regions of the 13–14 day old embryonic rat brain were injected into the hippocampus of adult rats which had previously been denervated of its serotoninergic input by 5,7-dihydroxytryptamine. At periods of up to 14 months after implantation, the brains were taken for immunohistochemical analysis of 5-hydroxytryptamine (5HT)-, substance P (SP)- and thyrotropin releasing hormone (TRH)-like immunoreactivity. Surviving grafts were found in all animals. The implants derived from mesencephalic raphé contained neurones immunoreactive to 5HT, SP or both substances together. On average 19% of the potential number of mesencephalic 5HT neurones were found in the grafts. Outgrowth of 5HT-immunoreactive fibres was extensive, and displayed the typical pattern of 5HT innervation in the normal hippocampus — the densest plexuses were found in the dentate gyrus, with sparser networks in the CA1 and CA2 regions. SP-positive processes were principally found only in the graft itself. Transplants of medullary raphé cells contained 5HT-immunoreactive neurones, some of which also contained SP- and/or TRH-like immunoreactivity, thereby mirroring the situation found in the caudal raphé complex in situ. An average of 18% of the total available medullary serotoninergic neurones were found at each graft site. A rich outgrowth of 5HT-immunoreactive varicose processes was evident, with the same pattern as the 5HT innervation by the mesencephalic raphé grafts, and as in the normal hippocampus. SP- and TRH-positive fibres were essentially detectable only in the graft, but not in the host hippocampus. The present studies indicate that the milieu of the hippocampus does not preferentially attenuate the survival of the serotoninergic cells which do not normally project to it. Nor is the fibre outgrowth of these medullary raphé 5HT neurones significantly different from that of the mesencephalic raphé. However, the hippocampal environment may be responsible for the appearance of SP-LI in the otherwise apparently solely 5HT-containing mesencephalic raphé neurones, and for repressing the outgrowth of fibres containing TRH-, or SP-like immunoreactivity, regardless of their origin.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-1106
    Keywords: Transplantation ; Medullary and mesencephalic raphé ; Host striatum ; Survival ; Transmitter phenotypy ; Target dependent fibre outgrowth ; Environmental regulation ; Substance P ; 5-Hydroxytryptamine ; Thyrotropin releasing hormone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Implants have been made of dissociated embryonic mesencephalic or medullary raphé cells into the adult rat striatum, previously depleted of its 5HT innervation. The transmitter complement and fibre outgrowth of the grafted neurones were analysed immunocytochemically. Serotonin-containing cells were found in both types of transplant, and the proportionate survival of the potential number of implanted 5HT cells was similar for each type of graft. However, these proportions were both greater than that described previously in transplants of mesencephalic raphé cells to the spinal cord. In addition, the proportionate survival of medullary substance P neurones grafted to the striatum was greater than that of medullary 5HT cells implanted in the same region. The transmitter complement of the medullary neurones was largely unaltered after transplantation. However, the mesencephalic grafts contained neurones storing 5HT- and/or substance P-, or TRH-like immunoreactivity. The 5HT/substance P and TRH neurones have so far not been encountered in the mesencephalon in situ using the present immunohistochemical methodology. Invasion of the host striatum by 5HT processes from the transplanted mesencephalic cells was extensive. Fibres from medullary raphé neurones, however, were restricted principally to within the graft itself. It is concluded that there may exist in the adult rat striatum a set of trophic factors for 5HT and substance P neurones different from those found in other regions of the central nervous system, such as spinal cord. Moreover, trophic agents in the host striatum appear to operate differentially on mesencephalic and medullary raphé 5HT neurones to regulate their axonal outgrowth. Lastly, the neurotransmitter phenotypic expression of the embryonic mesencephalic raphé cells may be susceptible to influences from the host environment.
    Type of Medium: Electronic Resource
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