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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 56 (1991), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Quantitative autoradiography was used to examine the distribution of [3H]phorbol 12,13 dibutyrate ([3HIPDBu) binding to protein kinase C in the middle frontal and temporal cortices and the hippocampal region of nine control and nine elderly subjects with Alzheimer's disease (AD). AD patients had a clinical diagnosis of the disease that was confirmed neuropathologically by the presence of numerous plaques in the hippocampus and cerebral cortex. Choline acetyltransferase (ChAT) activity was significantly reduced in the middle frontal and temporal cortex and in the hippocampus of AD subjects, with the deficit being 〉60% of control values. Quantitative autoradiographic analysis of [3H]PDBu binding to protein kinase C revealed a heterogeneous pattern in control brain, being particularly high in superficial layers of the cortex and CAI of the hippocampus. There were no significant differences between control and AD sections in all areas examined within the middle frontal cortex, e.g., layers 1–11 control, 491 ± 46 versus AD, 537 ± 39 pmol/g of tissue; middle temporal cortex, e.g., layers 1–11 control, 565 ± 68 versus AD, 465 ± 72 pmol/g of tissue; and hippocampal formation, e.g., CAI control, 51 ± 28 versus AD, 498 ± 25 pmol/g of tissue. In a parallel study, [3H]PDBu binding to homogenate preparations of control and AD brain confirmed that there was no significant difference in [3H]PDBu binding in either the particulate or the cytosolic fraction. We have demonstrated in a well-defined population of AD patients that [3H]PDBu binding to protein kinase C remains preserved in brain regions that are severely affected by the neuropathological and neurochemical correlates of AD.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 57 (1991), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Many of the neurotransmitter systems that are altered in senile dementia of the Alzheimer type are known to mediate their effects via G proteins, yet the integrity of guanine nucleotide-binding proteins (G proteins) in Alzheimer's diseased brains has received minimal investigation. The aim of this study was to establish whether the level of Gα subunits of five G proteins was altered in Alzheimer's disease. We used immunoblotting (Western blotting) to compare the amounts of Gi1, Gi2, GsH (heavy molecular weight), GSL (light molecular weight), and Go in the frontal cortex and hippocampus, two regions severely affected by the disease, and the cerebellum, which is less severely affected. The number of senile plaques was also quantified. We report that there was no significant difference in the level of these Gα subunits between Alzheimer's diseased and age-matched postmortem brains. These results suggest that alterations in the amount of G protein α subunits are not a feature of Alzheimer's disease.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 40 (1983), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The effects of the dopaminergic agonist apomorphine (1 mg-kg−1i.v.) upon local cerebral glucose utilization in 43 anatomically discrete regions of the CNS were examined in conscious, lightly restrained rats and in rats anesthetized with chloral hydrate by means of the quantitative autoradiographic [14C]2-deoxyglucose technique. In animals anesthetized with chloral hydrate, glucose utilization was reduced throughout all regions of the CNS from the levels observed in conscious animals, although the magnitude of the reductions in glucose use displayed considerable regional heterogeneity. With chloral hydrate anesthesia, the proportionately most marked reductions in glucose use (by 40–60% from conscious levels) were noted in primary auditory nuclei, thalmaic relay nuclei and neocortex and the least pronounced reductions in glucose use (by 15–25% from conscious levels) were observed in limbic areas, some motor relay nuclei and white matter. In conscious, lightly restrained rats, the administration of apomorphine (1 mg-kg−1) effected significant increases in glucose utilization in 15 regions of the CNS (e.g., subthalamic nucleus, ventral thalamic nucleus, rostral neocortex, substantia nigra, pars reticulata) and significant reductions in glucose utilization in two regions of the CNS (lateral habenular nucleus and anterior cingulate cortex). In rats anesthetized with chloral hydrate, the effects of apomorphine upon local glucose utilization were less widespread and less marked than in conscious animals. In only two of the regions (the globus pallidus and septal nucleus), which displayed increased glucose use following apomorphine in conscious rats, were significant increases in local glucose utilization observed with this agent in chloral hydrate-anesthetized rats. In the pars compacta of the substantia nigra, in which apomorphine increased glucose utilization in conscious animals, significant reductions in glucose utilization were observed following apomorphine in rats anesthetized with chloral hydrate. The profound effects of chloral hydrate anesthesia upon local cerebral glucose use and the modification by this anesthetic regime of the local metabolic responses to apomorphine, emphasize the difficulties which exist in the extrapolation of data from anesthetized animals to the conditions which prevail in the conscious animal.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 527 (1988), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science, Ltd
    European journal of neuroscience 15 (2002), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Heat shock protein (HSP70) a member of the 70 kDa HSP superfamily, has been widely implicated in the cellular stress response to numerous insults. HSP70 may be a significant factor in cell survival following stresses such as cerebral ischaemia. The precise mechanisms by which HSP70 facilitates cell survival remain unclear. The aim of this study was to ascertain whether any differences in local cerebral glucose utilization (LCGU) existed between transgenic mice overexpressing HSP70 (HSP70 Tg) and wild- type littermate (WT) mice. LCGU was assessed using 14C-2-deoxyglucose in HSP70 Tg and WT mice under basal conditions (intraperitoneal injection of saline) and during metabolic activation produced by NMDA receptor blockade (intraperitoneal injection of dizocilpine, 1 mg/kg). No significant alterations in LCGU were observed between saline injected HSP70 Tg and WT mice in any of the 35 brain regions analyzed. Dizocilpine injection produced significant heterogeneous alterations in LCGU in HSP70 Tg mice (24 of 35 brain regions) and in WT mice (22 of 35 brain regions) compared with saline injected mice. The distribution of altered LCGU produced by dizocilpine was similar in HSP70 Tg and WT mice. However in five brain regions, dizocilpine injected HSP70 Tg mice displayed significantly altered LCGU compared to dizocilpine injected WT mice (anterior thalamic nucleus +27%, dorsal CA1 stratum lacunosum molecularae+22%, dorsal CA1 stratum oriens+ 14%, superior olivary body −26%, and the nucleus of the lateral lemniscus −16%). These data highlight that while overexpression of HSP70 transgene does not significantly alter LCGU in the basal state, mice overexpressing the HSP70 transgene respond differently to metabolic stress produced by NMDA receptor blockade in some important brain regions.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Apolipoprotein E (apoE, protein; APOE, gene) is expressed as three isoforms in humans (E2, E3, E4). The APOE-ε4 allele is associated with a poor outcome in patients after head injury of which ischaemic brain damage is a contributor of mortality and morbidity. The aim of the study was to determine whether mice expressing human APOE-ε4 displayed more extensive ischaemic neuronal damage 72 h after transient global ischaemia compared with mice which express human APOE-ε3. APOE-ε3 and -ε4 transgenic mice, under the control of a human promoter, were used which express human APOE in neurons and glia. Ischaemic neuronal damage in the CA1 pyramidal cell layer in the APOE-ε4 transgenic mice was significantly greater than in the APOE-ε3 mice after global ischaemia (36.4 ± 8.9%, 18.2 ± 7.3%; P 〈 0.05). This was associated with more extensive neuronal apoE immunoreactivity in the CA1 pyramidal cell layer in the APOE-ε4 transgenic mice compared with APOE-ε3 transgenic mice. In contrast, in the caudate nucleus, there were similar levels of ischaemic neuronal damage in the APOE-ε3 and -ε4 transgenic mice (39.2 ± 10.1%; 44.6 ± 8.4%, P = 0.32). In the caudate, similar numbers of neurons were immunostained for apoE in the APOE-ε3 and -ε4 transgenic mice. The present study demonstrated that the APOE-ε4 allele is associated with an increased vulnerability of a specific brain region to the effects of global ischaemia, which is closely associated with an increase in neuronal apoE. The data extend previous work and are consistent with an association of the APOE-ε4 allele with a poor outcome after acute brain injury in humans.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: N-methyl-d-aspartate (NMDA) and non-NMDA receptor-mediated manipulations of the cortical cholinergic input arising from the basal forebrain differentially affect cognitive function. We used [14C]-2-deoxyglucose autoradiography in conscious rats to map the effects of excitatory amino acid agonist infusions into the nucleus basalis magnocellularis (NBM) on cerebral functional activity, as reflected by local rates of glucose utilization. Acute stimulation of NBM neurones by local infusion of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), 15 min before glucose use measurement, resulted in glucose use reductions in nine cortical regions innervated by NBM efferents including prefrontal, frontal, sensorimotor and cingulate cortices. NMDA infusions altered glucose use in two cortical areas. Both AMPA and NMDA markedly increased glucose use in the striatum and globus pallidus, with concomitant perturbations in striato-pallidal projection targets including the substantia nigra, entopeduncular nucleus, subthalamic nucleus and lateral habenular nucleus. In contrast, the GABAA agonist muscimol did not affect glucose use in the NBM or neocortical regions, but induced glucose use increases in several subcortical nuclei including the substantia nigra and entopeduncular nucleus.The delayed effects of excitotoxic lesions were assessed 3 weeks after basal forebrain infusions of AMPA, NMDA, ibotenate or quisqualate. Statistically significant glucose use changes only occurred in the hypothalamus after NMDA, and the NBM after ibotenate infusions, although reduced cortical metabolism was apparent following AMPA-induced lesions of the NBM. Results support a dissociation between the functional sequelae of NMDA and non-NMDA receptor-mediated events in the basal forebrain, and long-term compensatory functional adaptation following cortical denervation.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 39 (1982), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The dose-dependent effects of two putative γ-aminobutyric acid (GABA)-ergic agonists, muscimol and 4,5,6,7-tetrahydroisoxazolo(4,5-e)-pyridin-3-ol (THIP), upon local cerebral glucose utilisation in 60 discrete regions of the CNS have been examined in conscious rats using the [14C]2-deoxyglucose quantitative autoradiographic technique. The intravenous administration of muscimol (0.15-5 mg/kg) and THTP (1-10 mg/kg) resulted in a heterogeneous pattern of significantly reduced glucose utilisation throughout the CNS. The regional hierarchy of changes in glucose utilisation was similar for both muscimol and THIP in all regions (with the exception of the superior colliculus), with muscimol being approximately six times more potent in all regions investigated. The regions in which glucose utilisation was extremely sensitive to change, displaying reductions of approximately 40% following muscimol (1.5 mg/kg) or THIP (10 mg/kg) administration, included all layers of the neocortex (frontal, sensory motor, posterior parietal, primary auditory and visual cortices), the lateral portion of the caudate nucleus, and some thalamic nuclei (lateral geniculate body, mediodorsal and ventrolateral nuclei). Regions displaying more modest reductions in glucose utilisation, approximately 20% following muscirnol (1.5 mg/kg) and THTP (10 mg/kg) administration, included most extrapyramidal regions (substantia nigra, pars cornpacta and reticulata, globus pallidus, subthalamic nucleus, medial portion of the caudate nucleus), a number of cortical and subcortical limbic areas (cingulate and olfactory cortices, hippocampus, nucleus accumbens, anterior thalamus), and medial raphe nucleus. In contrast, in a large number of regions (including cerebellum and related nuclei such as the inferior olivary, red and vestibular nuclei, white matter, pontine reticular formation, hypothalamus, lateral habenula and amygdala), there were only minimal (approximately 10%) reductions in glucose utilisation following muscimol (1.5 mg/kg) and THIP (10 mg/kg) administration. In no region of the CNS was a significant increasc in glucose utilisation observed with any concentration of either muscirnol or THIP. The regional distribution of alterations in glucose utilisation following muscimol and THIP administration, which does not correspond to the known topography of GABAergic neurones and receptors, provides a comprehensive description of the functional alterations, as reflected in rates of glucose utilisation, that occur in conscious rats after systemic administration of these two putative GABAergic agonists.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 39 (1982), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Local rates of glucose utilization in 38 regions of the CNS were measured in conscious, lightly restrained rats during normothermia (rectal temperature, 37.4 ± 0.1°C), hypothermia (31.8 ± 0.1°C), and hyperthermia (40.2 ± 0.3°C). In 34 of the 38 regions examined (the four exceptions being primary auditory nuclei in the lower brainstem), a significant relationship could be demonstrated between the rate of glucose utilization and body temperature. The magnitude of temperature-related alterations in glucose use displayed considerable regional heterogeneity. In hypothermic rats the reductions in glucose use were proportionately most marked (reduced 35–50% from normothermic) in thalamic nuclei, extrapyramidal and motor areas, septohippocampal formation, and some areas of neocortex and white matter; they were least pronounced in anterior hypothalamus (reduced by 13%), habenula (by 16%), and amygdala (by 22%). In hyperthermic rats, significantly increased glucose utilization was observed in only 16 of the 38 areas examined (e.g., hypothalamus, hippocampus, extrapyramidal system, and raphe nucleus), whereas in a number of major areas (such as the neocortex and thalamus) glucose use was minimally altered with hyperthermia. The regional heterogeneity in the alterations in glucose utilization suggests that caution must be exercised in the interpretation of autoradiographic 2-deoxyglucose investigations in which body temperature disturbances occur.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] The technique using 14C-labelled 2-deoxyglucose for the measurement of the rates of local cerebral glucose utilisation7 offers a novel approach to study the pharmacology and physiology of the central nervous system (CNS). The energy requirements of cerebral tissue are derived mainly from the ...
    Type of Medium: Electronic Resource
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