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精神疾病中线粒体的动态变化:来自人类神经细胞模型的新机制见解。

Dynamic Changes of the Mitochondria in Psychiatric Illnesses: New Mechanistic Insights From Human Neuronal Models.

机构信息

Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.

出版信息

Biol Psychiatry. 2018 May 1;83(9):751-760. doi: 10.1016/j.biopsych.2018.01.007. Epub 2018 Jan 17.

Abstract

Mitochondria play a crucial role in neuronal function, especially in energy production, the generation of reactive oxygen species, and calcium signaling. Multiple lines of evidence have suggested the possible involvement of mitochondrial deficits in major psychiatric disorders, such as schizophrenia and bipolar disorder. This review will outline the current understanding of the physiological role of mitochondria and their dysfunction under pathological conditions, particularly in psychiatric disorders. The current knowledge about mitochondrial deficits in these disorders is somewhat limited because of the lack of effective methods to dissect dynamic changes in functional deficits that are directly associated with psychiatric conditions. Human neuronal cell model systems have been dramatically developed in recent years with the use of stem cell technology, and these systems may be key tools for overcoming this dilemma and improving our understanding of the dynamic changes in the mitochondrial deficits in patients with psychiatric disorders. We introduce recent discoveries from new experimental models and conclude the discussion by referring to future perspectives. We emphasize the significance of combining studies of human neuronal cell models with those of other experimental systems, including animal models.

摘要

线粒体在神经元功能中起着至关重要的作用,特别是在能量产生、活性氧物种的产生和钙信号转导方面。多条证据表明,线粒体缺陷可能与精神疾病有关,如精神分裂症和双相情感障碍。本综述将概述线粒体的生理作用及其在病理条件下(特别是在精神疾病中)的功能障碍。由于缺乏有效方法来剖析与精神状况直接相关的功能缺陷的动态变化,目前对这些疾病中线粒体缺陷的了解有些有限。近年来,随着干细胞技术的应用,人类神经元细胞模型系统得到了极大的发展,这些系统可能是克服这一困境和提高我们对精神疾病患者中线粒体缺陷动态变化理解的关键工具。我们介绍了来自新实验模型的最新发现,并通过参考未来的观点来结束讨论。我们强调了将人类神经元细胞模型的研究与包括动物模型在内的其他实验系统的研究相结合的重要性。

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