In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 93, No. 24 ( 1996-11-26), p. 14182-14187
Kurzfassung:
The pathophysiology of schizophrenia may involve
perturbations of synaptic organization during development. The presence of cytoarchitectural abnormalities that may reflect such perturbations
in the brains of patients with this disorder has been well-documented. Yet the mechanistic basis for these features of the disorder is still
unknown. We hypothesized that altered regulation of the neuronal growth-associated protein GAP-43, a membrane phosphoprotein found at
high levels in the developing brain, may play a role in the alterations in brain structure and function observed in schizophrenia. In the
mature human brain, GAP-43 remains enriched primarily in association cortices and in the hippocampus, and it has been suggested that this
protein marks circuits involved in the acquisition, processing, and/or storage of new information. Because these processes are known
to be altered in schizophrenia, we proposed that GAP-43 levels might be altered in this disorder. Quantitative immunoblots revealed that the
expression of GAP-43 is increased preferentially in the visual association and frontal cortices of schizophrenic patients, and that
these changes are not present in other neuropsychiatric conditions requiring similar treatments. Examination of the levels of additional
markers in the brain revealed that the levels of the synaptic vesicle protein synaptophysin are reduced in the same areas, but that the
abundance of the astrocytic marker of neurodegeneration, the glial fibrillary acidic protein, is unchanged. In situ hybridization histochemistry was used to show that the laminar pattern
of GAP-43 expression appears unaltered in schizophrenia. We propose that schizophrenia is associated with a perturbed organization of
synaptic connections in distinct cortical associative areas of the human brain, and that increased levels of GAP-43 are one manifestation
of this dysfunctional organization.
Materialart:
Online-Ressource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.93.24.14182
Sprache:
Englisch
Verlag:
Proceedings of the National Academy of Sciences
Publikationsdatum:
1996
ZDB Id:
209104-5
ZDB Id:
1461794-8
SSG:
11
SSG:
12
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