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  • 1
    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: Signalling through tyrosine kinase receptor B (trkB) influences neuronal survival, differentiation and synaptogenesis. trkB exists in a full-length form (trkBTK+), which contains a catalytic tyrosine kinase (TK) domain, and a truncated form (trkBTK–), which lacks this domain. In the rodent brain, expression of trkBTK+ decreases and trkBTK– increases during postnatal life. We hypothesized that both forms of trkB receptor mRNA would be present in the human neocortex and that the developmental profile of trkB gene expression in human may be distinct from that in rodent. We detected both trkBTK+ and trkBTK– mRNA in RNA extracted from multiple human brain regions by Northern blot. Using in situ hybridization, we found trkBTK+ mRNA in all cortical layers, with highest expression in layer IV and intermediate-to-high expression in layers III and V of the human dorsolateral prefrontal cortex. trkBTK+ mRNA was present in neurons with both pyramidal and nonpyramidal shapes in the dorsolateral prefrontal cortex. trkBTK+ mRNA levels were significantly increased in layer III in young adults as compared with infants and the elderly. In the elderly, trkBTK+ mRNA levels were reduced markedly in all cortical layers. Unlike the mRNA encoding the full-length form of trkB, trkBTK– mRNA was distributed homogeneously across the grey matter, and trkBTK– mRNA levels increased only slightly during postnatal life. The results suggest that neurons in the human dorsolateral prefrontal cortex are responsive to neurotrophins throughout postnatal life and that this responsiveness may be modulated during the human lifespan.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2072
    Keywords: Catalepsy ; Vacuous chewing movements ; Parkinsonism ; Tardive dyskinesia ; Haloperidol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Patients who develop persistent parkinsonism while on chronic neuroleptic therapy may be predisposed towards the development of tardive dyskinesia (TD). We investigated this issue in an animal model of TD by examining the association between catalepsy and the syndrome of neuroleptic-induced vacuous chewing movements (VCMs). VCMs were measured every 3 weeks for 33 weeks while rats received injections of haloperidol decanoate. Catalepsy was measured after the second through the seventh injections of the depot neuroleptic. There were no correlations between the severity of catalepsy scores after the second or third injections of haloperidol and the severity of the overall VCM syndrome. However, the severity of the catalepsy score following the third through seventh injections of haloperidol strongly correlated with the concurrent number of VCMs. Persistent high catalepsy scores across the six catalepsy rating sessions were strongly associated with the development of persistent severe VCMs. These findings suggest that, to the extent that persistent parkinsonian signs in humans are associated with a propensity towards the development of TD, the VCM syndrome in rats is at least a partially faithful animal model of this relationship.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1435-1463
    Keywords: Autoradiography ; neurotensin ; schizophrenia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Neurotensin, an endogenous peptide and putative neurotransmitter, exhibits a wide range of interactions with dopaminergic neurons and displays some actions akin to neuroleptics. Moreover, neurotensin receptors are abundant in specific layers of the entorhinal cortex where cytoarchitectural abnormalites have been reported in schizophrenia. We therefore examined the entorhinal cortex from postmortem specimens of five control patients and six schizophrenic patients for alterations in neurotensin receptor quantitation and distribution using receptor autoradiography. Specific125I-neurotensin binding was concentrated in layer II cell clusters, with a 40% reduction in binding in the schizophrenic group (p〈0.05). Moderate binding was observed in both cohorts in deep layers V/VI, with negligible binding in the hippocampus. There was no statistical difference in quantitative neurotensin binding in other lamina of the entorhinal cortex of schizophrenics compared with controls. The characteristic laminar pattern of binding did not differ between cohorts. The reduction in neurotensin binding in schizophrenics is consistent with an increasing number of reports of structural abnormalities in the medial temporal lobe of schizophrenics in general and the entorhinal cortex in particular. Further studies are required to examine the evidence for neuroanatomic and neurochemical pathology in the entorhinal cortex.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1573-6903
    Keywords: Ca2+ transport ; Na+-Ca2+ exchange ; human brain ; synaptic membranes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Procedures were developed for measurement of Na+/Ca2+ exchange in resealed plasma membrane vesicles from postmortem human brain. The vesicle preparation method permits use of stored frozen tissue with minimal processing required prior to freezing. Vesicles prepared in this manner transport Ca2+ in the presence of a Na+ gradient. The kinetic characteristics of the Na+/Ca2+ exchange process were determined in membrane vesicles isolated from hippocampus and cortex. The Kact for Ca2+ was estimated to be 32 μM for hippocampal and 17 μM for cortical tissue. The maximal rate of Ca2+ uptake (Vmax) was 3.5 nmol/mg protein/15 sec and 3.3 nmol/mg protein/15 sec for hippocampal and cortical tissue, respectively. Exchange activity was dependent on the Na+ gradient, and was optimal in the high pH range. Therefore, membranes in which Na+-dependent o Ca2+ transport activity is preserved can be isolated from postmortem human brain and could be used to determine the influence of pathological conditions on this transport system.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1573-6903
    Keywords: Alcoholism ; glutamate receptors ; NMDA receptors ; glutamate binding ; seizures ; hippocampus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Brains from human alcoholics and non-alcoholics were obtained shortly after death. The hippocampus was dissected, homogenized, and processed for the isolation of a synaptic membraneenriched fraction and the study ofl-[3H]glutamic acid and 3-((±)-2-carboxypiperazin-4-yl)-[1,23H]propyl-l-phosphonic acid ([3H]CPP) binding sites. The pharmacological characteristics ofl-[3H]glutamic acid binding to synaptic membranes isolated from hippocampus corresponded to the labeling of a mixture of N-methyl-d-aspartate (NMDA), kainate and quisqualic acid receptor sites. Synaptic membranes prepared from the hippocampus of individuals classified as alcoholics had significantly higher density of glutamate binding sites than identically prepared membranes from non-alcoholic individuals. In addition, there was a clear definition of a population ofl-glutamate binding sites (approx. 10% of total) in the membranes from alcoholics that had a higher affinity for the ligand than the major set of sites labeled in membranes from both alcoholics and non-alcoholics. Neither the age of the individuals at the time of death nor the time that elapsed between death and processing of brain tissue were significant factors in determining either recovery of purified synaptic membranes from brain homogenates orl-[3H]glutamate binding to synaptic membranes. In order to determine whether some of the changes inl-[3H]glutamic acid binding were due to alterations in binding at the NMDA receptor subtype, we also measured binding of [3H]CPP to extensively washed crude synaptosomal membranes. Membranes from brains of alcoholics had higher affinity (3-fold) for [3H]CPP but lower binding capacity (3-fold) when compared with those of non-alcoholics. These observations suggest selective changes among different glutamate receptor subtypes in human brain under conditions of chronic alcohol intake.
    Type of Medium: Electronic Resource
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