Mitochondrial complex I subunits expression is altered in schizophrenia: A postmortem study
Mitochondrial complex I subunits expression is altered in schizophrenia: A postmortem study
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DOI：
10.1016/j.biopsych.2003.12.012
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发表时间：
2004-04-01
影响因子：
10.6
通讯作者：
Ben Shachar, D
中科院分区：
文献类型：
--
作者：
Karry, R;Klein, E;Ben Shachar, D
背景：一些独立的证据表明，精神分裂症患者的大脑和外周存在线粒体功能障碍，包括线粒体发育不全、氧化磷酸化系统功能障碍和线粒体相关基因表达改变。在这项研究中，我们分析了线粒体复合体I的三个亚基在mRNA和蛋白质水平上的变化，这些脑组织标本来自精神分裂症、重度抑郁症、双相情感障碍和正常对照的患者的前额叶和腹侧顶枕皮层。与正常对照组相比，精神分裂症患者前额叶皮层复合体I的24-kDa和51-kDa亚基mRNA和蛋白水平均显著降低，而枕顶腹侧皮层复合体I的mRNA和蛋白水平均升高。在后一区域，两种亚基的蛋白水平在双相患者中也有所增加，这与精神分裂症和双相患者的临床症状有显著重叠是一致的。前额皮质75-kDa亚基表达未见明显变化。结论：前额叶皮层复合体I亚基的减少与精神分裂症最突出的缺陷之一，即前额叶功能低下相一致，从而进一步支持该疾病线粒体功能障碍的假设。复合体I在不同大脑区域的异常双向表达，而不是在一个限定的区域，支持了精神分裂症患者大脑回路受损的观点。
Background: Several independent lines of evidence indicate mitochondrial dysfunction in schizophrenia in the brain and periphery, including mitochondrial hypoplasia, dysfunction of the oxidative phosphorylation system, and altered mitochondrial-related gene expression.Methods. In this study, three subunits of mitochondrial complex I were analyzed at the level of mRNA and protein in postmortem brain specimens from the prefrontal and the ventral parietooccipital cortex of patients with schizophrenia, major depression, bipolar disorder, and normal control subjects.Results. Both mRNA and protein levels of the 24-kDa and 51-kDa subunits of complex I were significantly decreased in the prefrontal cortex, but increased in the ventral parietooccipital cortices of schizophrenia patients compared with normal control subjects. In the latter region, protein levels of both subunits were increased in bipolar patients as well, being in line with the significant overlap in clinical symptoms between schizophrenia and bipolar patients. No change was observed in the 75-kDa subunit expression in the prefrontal cortex.Conclusions: The schizophrenia-specific reduction in complex I subunits in the Prefrontal cortex is consistent with one of schizophrenia's most prominent deficits, namely, hypofrontality, thus further supporting the hypothesis of mitochondrial dysfunction in this disorder. The abnormal, bidirectional expression of complex I in various brain regions, rather than in a circumscribed area, supports the idea of impaired cerebral circuitry in schizophrenia.