Abnormalities in Mitochondrial Structure in Cells from Patients with Bipolar Disorder
Abnormalities in Mitochondrial Structure in Cells from Patients with Bipolar Disorder
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DOI：
10.2353/ajpath.2010.081068
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发表时间：
2010-08-01
影响因子：
6
通讯作者：
Cohen, Bruce M.
中科院分区：
文献类型：
--
作者：
Cataldo, Anne M.;McPhie, Donna L.;Cohen, Bruce M.
尸检、遗传学、脑成像和外周细胞研究都支持线粒体活性降低是双相情感障碍（BD）表现的一个因素。由于异常的线粒体形态通常与能量代谢的改变有关，我们研究了BD患者的脑和外周细胞中是否存在线粒体结构的变化。与精神健康的年龄匹配的对照组相比，BD患者的线粒体显示出大小和分布异常。具体而言，在大脑中，单个线粒体分布平均而言在BD样品中具有显著较小的面积（P = 0.03）。在外周细胞中，BD样本中的线粒体在核周区域比在远端突起中更成比例地集中（P = 0.0008）。这些线粒体变化似乎与锂暴露无关。此外，脑和外周细胞的这些异常与线粒体相互作用的肌动蛋白或微管蛋白细胞骨架的实质性变化无关。观察到的线粒体大小和分布的变化可能与能量缺乏有关，因此可能对BD患者的细胞可塑性，弹性和存活率产生影响，特别是在具有高能量需求的大脑中。这些发现可能对诊断有意义，如果它们是BD特异性的，如果它们提供了BD潜在病理生理学的线索，则对治疗有意义。(Am J Pathol 2010，177：575-585; DOI：10.2353/ajpath.2010.081068）
Postmortem, genetic, brain imaging, and peripheral cell studies all support decreased mitochondrial activity as a factor in the manifestation of Bipolar Disorder (BD). Because abnormal mitochondrial morphology is often linked to altered energy metabolism, we investigated whether changes in mitochondrial structure were present in brain and peripheral cells of patients with BD. Mitochondria from patients with BD exhibited size and distributional abnormalities compared with psychiatrically-healthy age-matched controls. Specifically, in brain, individual mitochondria profiles had significantly smaller areas, on average, in BD samples (P = 0.03). In peripheral cells, mitochondria in BD samples were concentrated proportionately more within the perinuclear region than in distal processes (P = 0.0008). These mitochondrial changes did not appear to be correlated with exposure to lithium. Also, these abnormalities in brain and peripheral cells were independent of substantial changes in the actin or tubulin cytoskeleton with which mitochondria interact. The observed changes in mitochondrial size and distribution may be linked to energy deficits and, therefore, may have consequences for cell plasticity, resilience, and survival in patients with BD, especially in brain, which has a high-energy requirement. The findings may have implications for diagnosis, if they are specific to BD, and for treatment, if they provide clues as to the underlying pathophysiology of BD. (Am J Pathol 2010, 177:575-585; DOI: 10.2353/ajpath.2010.081068)