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  • 1
    ISSN: 1432-0568
    Keywords: Afferent projections ; HRP ; WGA ; Lateral reticular nucleus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The organization of the afferent projections to the lateral reticular nucleus of the rat was investigated following placement of horseradish peroxidase-conjugated wheatgerm agglutinin into the red nucleus, fastigial nucleus, various levels of the spinal cord or the sensorimotor area of the cerebral cortex. The pattern of distribution of anterogradely labelled profiles visualized with tetramethylbenzidine revealed that the caudal three-fourths of the lateral reticular nucleus received a large, topographically organized projection from the entire length of the contralateral spinal cord. The lateral part of the rostral half of the lateral reticular nucleus received a small projection from the contralateral red nucleus, the dorsal part of the middle third of the nucleus received a diffuse projection from the contralateral fastigial nucleus, and the extreme rostromedial part of the nucleus received a sparse projection from the contralateral cerebral cortex. The dorsal part of the middle third of the lateral reticular nucleus also received a small projection from the ipsilateral cervical spinal cord. The distribution of afferent fibres from different levels of the spinal cord, red nucleus, and fastigial nucleus overlapped substantially in the middle third of the lateral reticular nucleus, whereas the cerebral cortical receiving area was separate. These data suggest that the middle third of the lateral reticular nucleus integrates spinal and supraspinal impulses to the cerebellum, while the rostral part of the nucleus is involved in a separate cerebral cortico-cerebellar pathway.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Protein kinase B and glycogen synthase kinase-3 have been identified as susceptibility genes for schizophrenia and altered protein and mRNA levels have been detected in the brains of schizophrenics post-mortem. Recently, we reported that haloperidol, clozapine and risperidone alter glycogen synthase kinase-3 and β-catenin protein expression and glycogen synthase kinase-3 phosphorylation levels in the rat prefrontal cortex and striatum. In the current study, β-catenin, adenomatous polyposis coli, Wnt1, dishevelled and glycogen synthase kinase-3 were examined in the ventral midbrain and hippocampus using western blotting. In addition, β-catenin and GSK-3 were examined in the substantia nigra and ventral tegmental area using confocal and fluorescence microscopy. The results indicate that repeated antipsychotic administration results in significant elevations in glycogen synthase kinase-3, β-catenin and dishevelled-3 protein levels in the ventral midbrain and hippocampus. Raclopride causes similar changes in β-catenin and GSK-3 in the ventral midbrain, suggesting that D2 dopamine receptor antagonism mediated the changes observed following antipsychotic administration. In contrast, amphetamine, a drug capable of inducing psychotic episodes, had the opposite effect on β-catenin and GSK-3 in the ventral midbrain. Collectively, the results suggest that antipsychotics may exert their beneficial effects through modifications to proteins that are associated with the canonical Wnt pathway.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Calcineurin (CN) was recently identified as a susceptibility gene for schizophrenia as well as showing altered RNA expression levels in the post-mortem brains of individuals with schizophrenia. CN knockout mice show a number of behaviours associated with schizophrenia, including deficits in sensorimotor gating, suggesting a link between CN and psychosis. Concurrently, we found, using genome screening techniques, that antipsychotics alter CN expression levels. Therefore, western blotting, in situ hybridization, immunocytochemistry and phosphatase assays were employed to determine what effect antipsychotics have on CN. The results indicate that clozapine, risperidone and haloperidol cause substantial reductions in the A subunit of CN but not CN B at both the RNA and protein levels in the striatum and prefrontal cortex. The changes could only be observed after repeated treatment with antipsychotics but not after acute administration. The alterations in CN protein levels were specific to antipsychotics and mediated by D2 dopamine receptor antagonism. However, despite reductions in CN protein levels, the phosphatase activity of CN was significantly elevated after treatment with antipsychotics. Collectively the results suggest that CN may be a common target for antipsychotics and that antipsychotic-induced alterations in CN may represent one of the mechanisms by which antipsychotics alleviate psychosis.
    Type of Medium: Electronic Resource
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