a Department of Psychiatry and Behavioral Neurobiology , University of Alabama at Birmingham , Birmingham , AL , USA.
World J Biol Psychiatry. 2017 Dec;18(8):592-603. doi: 10.1080/15622975.2016.1197423. Epub 2016 Jul 11.
Recent evidences suggest that mitochondrial dysfunction maybe involved in the pathophysiology of major depressive disorder (MDD); however, the role of mitochondrial genes in this disorder has not been studied systematically. In the present study, we profiled expression of mitochondrial genes in dorsolateral prefrontal cortex (dlPFC) of MDD and non-psychiatric control subjects.
Human mitochondrial RT profile PCR array plates were used to examine differentially expressed genes in dlPFC of 11 MDD and 11 control subjects. Differentially expressed genes were validated independently by qRT-PCR. Biological relevance of differentially expressed genes was analysed by gene ontology (GO) and ingenuity pathways analysis (IPA).
We found that 16 genes were differentially expressed in the MDD group compared with control group. Among them, three genes were downregulated and 13 genes upregulated. None of these genes were affected by confounding variables, such as age, post-mortem interval, brain pH, and antidepressant toxicology. Seven differentially expressed genes were successfully validated in MDD subjects. GO and IPA analyses identified several new regulatory networks associated with mitochondrial dysfunctions in MDD.
Our findings suggest abnormal mitochondrial systems in the brain of MDD subjects which could be involved in the etiopathogenesis of this disorder.
最近的证据表明,线粒体功能障碍可能与重度抑郁症(MDD)的病理生理学有关;然而,线粒体基因在这种疾病中的作用尚未被系统研究。在本研究中,我们对 MDD 和非精神病对照受试者的背外侧前额叶皮质(dlPFC)中线粒体基因的表达进行了分析。
使用人类线粒体 RT 谱 PCR 阵列板检测 11 名 MDD 和 11 名对照受试者 dlPFC 中差异表达的基因。通过 qRT-PCR 独立验证差异表达的基因。通过基因本体论(GO)和 ingenuity 通路分析(IPA)分析差异表达基因的生物学相关性。
与对照组相比,我们发现 MDD 组中有 16 个基因表达差异。其中,有 3 个基因下调,13 个基因上调。这些基因均不受年龄、死后间隔、脑 pH 值和抗抑郁药毒理学等混杂变量的影响。在 MDD 患者中成功验证了 7 个差异表达基因。GO 和 IPA 分析确定了与 MDD 中线粒体功能障碍相关的几个新的调控网络。
我们的研究结果表明,MDD 患者大脑中线粒体系统异常,这可能与该疾病的发病机制有关。