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Region and diagnosis-specific changes in synaptic proteins in schizophrenia and bipolar I disorder

Version 2 2024-06-04, 10:18
Version 1 2015-08-17, 15:36
journal contribution
posted on 2024-06-04, 10:18 authored by Laura GrayLaura Gray, B Dean, HC Kronsbein, PJ Robinson, E Scarr
Aberrant regulation of synaptic function is thought to play a role in the aetiology of psychiatric disorders, including schizophrenia and bipolar disorder. Normal neurotransmitter release is dependent on a complex group of presynaptic proteins that regulate synaptic vesicle docking, membrane fusion and fission, including synaptophysin, syntaxin, synaptosomal-associated protein-25 (SNAP-25), vesicle-associated membrane protein (VAMP), α-synuclein and dynamin I. In addition, structural and signalling proteins such as neural cell adhesion molecule (NCAM) maintain the integrity of the synapse. We have assessed the levels of these important synaptic proteins using Western blots, in three cortical regions (BA10, 40 and 46) obtained post-mortem from subjects with bipolar 1 disorder, schizophrenia or no history of a psychiatric disorder. In bipolar 1 disorder cortex (parietal; BA40), we found a significant increase in the expression of SNAP-25, and a significant reduction in α-synuclein compared with controls. These changes in presynaptic protein expression are proposed to inhibit synaptic function in bipolar 1 disorder. In schizophrenia, a significant reduction in the ratio of the two major membrane-bound forms of NCAM (180 and 140) was observed in BA10. The distinct functions of these two NCAM forms suggest that changes in the comparative levels of these proteins could lead to a destabilisation of synaptic signalling. Our data support the notion that there are complex and region-specific alterations in presynaptic proteins that may lead to alterations in synaptic activity in both schizophrenia and bipolar disorder.

History

Journal

Psychiatry research

Volume

178

Pagination

374-380

Location

Amsterdam, The Netherlands

ISSN

1872-7123

Language

eng

Publication classification

C Journal article, C1.1 Refereed article in a scholarly journal

Copyright notice

2010, Elsevier

Issue

2

Publisher

Elsevier

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