Babenko Vladimir N, Smagin Dmitry A, Kudryavtseva Natalia N
Modeling Neuropathology Laboratory, Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk, Russia.
J Integr Bioinform. 2017 Sep 13;14(3):20170024. doi: 10.1515/jib-2017-0024.
ApoE expression status was proved to be a highly specific marker of energy metabolism rate in the brain. Along with its neighbor, Translocase of Outer Mitochondrial Membrane 40 kDa (TOMM40) which is involved in mitochondrial metabolism, the corresponding genomic region constitutes the neuroenergetic hotspot. Using RNA-Seq data from a murine model of chronic stress a significant positive expression coordination of seven neighboring genes in ApoE locus in five brain regions was observed. ApoE maintains one of the highest absolute expression values genome-wide, implying that ApoE can be the driver of the neighboring gene expression alteration observed under stressful loads. Notably, we revealed the highly statistically significant increase of ApoE expression in the hypothalamus of chronically aggressive (FDR < 0.007) and defeated (FDR < 0.001) mice compared to the control. Correlation analysis revealed a close association of ApoE and proopiomelanocortin (Pomc) gene expression profiles implying the putative neuroendocrine stress response background of ApoE expression elevation therein.
载脂蛋白E(ApoE)的表达状态被证明是大脑能量代谢率的高度特异性标志物。与其相邻的参与线粒体代谢的线粒体外膜转位酶40 kDa(TOMM40)一起,相应的基因组区域构成了神经能量热点。利用慢性应激小鼠模型的RNA测序数据,在五个脑区中观察到ApoE基因座中七个相邻基因的显著正表达协同作用。ApoE在全基因组中保持着最高的绝对表达值之一,这意味着ApoE可能是在应激负荷下观察到的相邻基因表达改变的驱动因素。值得注意的是,我们发现与对照组相比,慢性攻击性(FDR < 0.007)和战败(FDR < 0.001)小鼠下丘脑ApoE表达有高度统计学意义的增加。相关性分析揭示了ApoE与阿黑皮素原(Pomc)基因表达谱密切相关,这意味着ApoE表达升高可能存在神经内分泌应激反应背景。