Mitochondrial dysfunction and pathology in bipolar disorder and schizophrenia.

Mitochondrial dysfunction and pathology in bipolar disorder and schizophrenia.
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DOI:
10.1016/j.ijdevneu.2010.08.007
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发表时间:
2011-05
影响因子:
1.8
通讯作者:
Konradi, Christine
Konradi, Christine
中科院分区:
医学4区
文献类型:
--
作者:
Clay, Hayley B.;Sillivan, Stephanie;Konradi, Christine

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双相情感障碍(BPD)和精神分裂症(SZ)是严重的精神疾病,总患病率为4%。在这些疾病中经常观察到能量代谢障碍。一些证据表明线粒体的潜在功能障碍:i)线粒体呼吸减少;(Ii)线粒体形态发生变化;iii)线粒体DNA(MtDNA)多态增加,mtDNA突变水平增加;iv)参与线粒体呼吸的核mRNA分子和蛋白质下调;v)高能磷酸盐减少,脑内pH降低;vi)精神症状和情感症状,以及线粒体疾病中的认知能力下降。此外,线粒体DNA聚合酶突变的转基因小鼠表现出类似情绪障碍的表型。在这篇综述中,我们将讨论线粒体的遗传和生理成分,以及在BPD和SZ中线粒体异常的证据。我们将进一步描述线粒体在脑发育中的作用,以及目前治疗精神疾病的药物对线粒体功能的影响。了解线粒体在发育和患病大脑中的作用,对于阐明精神疾病的病理生理机制至关重要。
Bipolar disorder (BPD) and schizophrenia (SZ) are severe psychiatric illnesses with a combined prevalence of 4%. A disturbance of energy metabolism is frequently observed in these disorders. Several pieces of evidence point to an underlying dysfunction of mitochondria: i) decreased mitochondrial respiration; (ii) changes in mitochondrial morphology; iii) increases in mitochondrial DNA (mtDNA) polymorphisms and in levels of mtDNA mutations; iv) downregulation of nuclear mRNA molecules and proteins involved in mitochondrial respiration; v) decreased high-energy phosphates and decreased pH in the brain; and vi) psychotic and affective symptoms, and cognitive decline in mitochondrial disorders. Furthermore, transgenic mice with mutated mitochondrial DNA polymerase show mood disorder-like phenotypes. In this review, we will discuss the genetic and physiological components of mitochondria and the evidence for mitochondrial abnormalities in BPD and SZ. We will furthermore describe the role of mitochondria during brain development and the effect of current drugs for mental illness on mitochondrial function. Understanding the role of mitochondria, both developmentally as well as in the ailing brain, is of critical importance to elucidate pathophysiological mechanisms in psychiatric disorders.
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