当前位置:首页 > 生物研究 > 神经生物学 > 正文

蛋白“Shn-2”缺失可导致统合失调症

蛋白“Shn-2”缺失可导致统合失调症

日本藤田保健卫生大学、日本理化研究所和日本大学等机构的联合研究小组日前宣称,他们发现实验鼠体内如果缺乏一种蛋白质,就会出现与人类统合失调症类似的症状。这一发现将有助于开发新的预防和治疗统合失调症的方法。相关研究发表在近期出版的美国《神经心理药物学》(Neuropsychopharmacology)杂志网络版上。

所谓统合失调症,是指外部的感觉刺激信息不能在人的中枢神经系统进行有效组合,从而使整个机体不能和谐运作,出现认知障碍和妄想、幻觉等。

有一种蛋白质“Shn-2”负责控制与免疫相关的基因群。研究人员通过基因操作使实验鼠不产生这种蛋白质。结果发现,实验鼠大脑出现慢性炎症,负责学习和记忆的部分也发育不足,出现类似统合失调症的症状。

研究人员连续三周给这种实验鼠投放具有抗炎作用的药物,发现其记忆及行动异常出现改善。研究人员表示,下一步将继续以这种实验鼠为对象,调查有助于改善症状的药物和食物。

了解更多:

Deficiency of Schnurri-2, an MHC Enhancer Binding Protein, Induces Mild Chronic Inflammation in the Brain and Confers Molecular, Neuronal, and Behavioral Phenotypes Related to Schizophrenia

Neuropsychopharmacology, 6 February 2013 | doi: 10.1038/npp.2013.38

Schnurri-2 (Shn-2), an NF-kappa B site-binding protein, tightly binds to the enhancers of major histocompatibility complex (MHC) class I genes and inflammatory cytokines, which have been shown to harbor common variant single nucleotide polymorphisms associated with schizophrenia. Although genes related to immunity are implicated in schizophrenia, there has been no study showing that their mutation or knockout results in schizophrenia. Here, we show that Shn-2 knockout mice have behavioral abnormalities that resemble those of schizophrenics. The mutant brain demonstrated multiple schizophrenia-related phenotypes, including transcriptome/proteome changes similar to those of postmortem schizophrenia patients, decreased parvalbumin and GAD67 levels, increased theta power on electroencephalograms, and a thinner cortex. Dentate gyrus granule cells failed to mature in mutants, a previously proposed endophenotype of schizophrenia. Shn-2 knockout mice also exhibited mild chronic inflammation of the brain, as evidenced by increased inflammation markers (including GFAP and NADH/NADPH oxidase p22 phox), and genome-wide gene expression patterns similar to various inflammatory conditions. Chronic administration of anti-inflammatory drugs reduced hippocampal GFAP expression, and reversed deficits in working memory and nest building behaviors in Shn-2 KO mice. These results suggest that genetically-induced changes in immune system can be a predisposing factor in schizophrenia.

阅读次数:  
更多 相关资讯:
    无相关信息

发表评论