Region and diagnosis-specific changes in synaptic proteins in schizophrenia and bipolar I disorder
Region and diagnosis-specific changes in synaptic proteins in schizophrenia and bipolar I disorder
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DOI：
10.1016/j.psychres.2008.07.012
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发表时间：
2010-07-30
影响因子：
11.3
通讯作者：
Scarr, Elizabeth
中科院分区：
文献类型：
--
作者：
Gray, Laura J.;Dean, Brian;Scarr, Elizabeth
突触功能的异常调节被认为在精神疾病的病因学中起作用，包括精神分裂症和双相情感障碍。正常的神经递质释放依赖于调节突触囊泡对接、膜融合和分裂的一组复杂的突触前蛋白，包括突触泡蛋白、突触融合蛋白、突触体相关蛋白-25（SNAP-25）、囊泡相关膜蛋白（VAMP）、α-突触核蛋白和动力蛋白I。此外，结构和信号蛋白如神经细胞粘附分子（NCAM）维持突触的完整性。我们已经评估了这些重要的突触蛋白的水平，使用蛋白质印迹，在三个皮质区域（BA 10，40和46）获得死后从受试者与双相1型精神障碍，精神分裂症或无精神疾病史。在双相1型障碍皮层（顶叶; BA 40），我们发现SNAP-25的表达显著增加，α-突触核蛋白与对照组相比显著减少。突触前蛋白表达的这些变化被认为抑制了双相1型障碍的突触功能。在精神分裂症中，在BA 10中观察到NCAM的两种主要膜结合形式（180和140）的比率显著降低。这两种NCAM形式的不同功能表明，这些蛋白质的比较水平的变化可能导致突触信号的不稳定。我们的数据支持的概念，有复杂的和区域特异性的突触前蛋白质的改变，可能会导致突触活动的精神分裂症和双相情感障碍的改变。(C)2008爱思唯尔爱尔兰有限公司版权所有，
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), a-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 postmortem 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 a-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. (C) 2008 Elsevier Ireland Ltd. All rights reserved,