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精神分裂症和双相情感障碍患者脑标本背外侧前额叶皮质中突触结合蛋白II基因表达:终生服用抗精神病药物的影响

Synapsin II gene expression in the dorsolateral prefrontal cortex of brain specimens from patients with schizophrenia and bipolar disorder: effect of lifetime intake of antipsychotic drugs.

作者信息

Tan M L, Dyck B A, Gabriele J, Daya R P, Thomas N, Sookram C, Basu D, Ferro M A, Chong V Z, Mishra R K

机构信息

Department of Psychiatry and Behavioural Neurosciences, McMaster UniversityHamilton, Ontario, Canada.

出版信息

Pharmacogenomics J. 2014 Feb;14(1):63-9. doi: 10.1038/tpj.2013.6. Epub 2013 Mar 26.

Abstract

Synapsins are neuronal phosphoproteins crucial to regulating the processes required for normal neurotransmitter release. Synapsin II, in particular, has been implied as a candidate gene for schizophrenia. This study investigated synapsin II mRNA expression, using real-time reverse transcriptase-PCR, in coded dorsolateral prefrontal cortical samples provided by the Stanley Foundation Neuropathology Consortium. Synapsin IIa was decreased in patients with schizophrenia when compared with both healthy subjects and patients with bipolar disorder, whereas synapsin IIb was only significantly reduced in patients with schizophrenia when compared with healthy subjects but not in patients with bipolar disorder. Furthermore, lifetime antipsychotic drug use was positively associated with synapsin IIa expression in patients with schizophrenia. Results suggest that impairment of synaptic transmission by synapsin II reduction may contribute to dysregulated convergent molecular mechanisms, which result in aberrant neural circuits that characterize schizophrenia, while implicating involvement of synapsin II in therapeutic mechanisms of currently prescribed antipsychotic drugs.

摘要

突触结合蛋白是对调节正常神经递质释放所需过程至关重要的神经元磷蛋白。特别是突触结合蛋白II,已被认为是精神分裂症的候选基因。本研究使用实时逆转录聚合酶链反应,对斯坦利基金会神经病理学联盟提供的编码背外侧前额叶皮质样本中的突触结合蛋白II mRNA表达进行了研究。与健康受试者和双相情感障碍患者相比,精神分裂症患者的突触结合蛋白IIa减少,而突触结合蛋白IIb仅在与健康受试者相比时在精神分裂症患者中显著降低,在双相情感障碍患者中则未降低。此外,精神分裂症患者终生使用抗精神病药物与突触结合蛋白IIa表达呈正相关。结果表明,突触结合蛋白II减少导致的突触传递受损可能导致分子机制失调,从而导致精神分裂症所特有的异常神经回路,同时提示突触结合蛋白II参与了目前处方抗精神病药物的治疗机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecb6/3970980/a7168a29a7a6/nihms4109f1a.jpg

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