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大规模DNA微阵列分析显示,双相情感障碍或精神分裂症患者死后大脑中线粒体相关基因的表达发生改变。

Altered expression of mitochondria-related genes in postmortem brains of patients with bipolar disorder or schizophrenia, as revealed by large-scale DNA microarray analysis.

作者信息

Iwamoto Kazuya, Bundo Miki, Kato Tadafumi

机构信息

Laboratory for Molecular Dynamics of Mental Disorders, Brain Science Institute, RIKEN, Wako, Saitama, Japan.

出版信息

Hum Mol Genet. 2005 Jan 15;14(2):241-53. doi: 10.1093/hmg/ddi022. Epub 2004 Nov 24.

Abstract

Accumulating evidence suggests that mitochondrial dysfunction underlies the pathophysiology of bipolar disorder (BD) and schizophrenia (SZ). We performed large-scale DNA microarray analysis of postmortem brains of patients with BD or SZ, and examined expression patterns of mitochondria-related genes. We found a global down-regulation of mitochondrial genes, such as those encoding respiratory chain components, in BD and SZ samples, even after the effect of sample pH was controlled. However, this was likely due to the effects of medication. Medication-free patients with BD showed tendency of up-regulation of subset of mitochondrial genes. Our findings support the mitochondrial dysfunction hypothesis of BD and SZ pathologies. However, it may be the expression changes of a small fraction of mitochondrial genes rather than the global down-regulation of mitochondrial genes. Our findings warrant further study of the molecular mechanisms underlying mitochondrial dysfunction in BD and SZ.

摘要

越来越多的证据表明,线粒体功能障碍是双相情感障碍(BD)和精神分裂症(SZ)病理生理学的基础。我们对BD或SZ患者的死后大脑进行了大规模DNA微阵列分析,并检测了线粒体相关基因的表达模式。我们发现,即使在样本pH值的影响得到控制后,BD和SZ样本中线粒体基因(如编码呼吸链成分的基因)仍普遍下调。然而,这可能是药物作用的结果。未服用药物的BD患者显示出线粒体基因子集上调的趋势。我们的研究结果支持BD和SZ病理的线粒体功能障碍假说。然而,可能是一小部分线粒体基因的表达变化,而非线粒体基因的普遍下调。我们的研究结果值得进一步研究BD和SZ中线粒体功能障碍的分子机制。

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