Exposure to different early-life stress experiences results in differentially altered DNA methylation in the brain and immune system.
Exposure to different early-life stress experiences results in differentially altered DNA methylation in the brain and immune system.
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不同的早期生活压力经历会导致大脑和免疫系统中 DNA 甲基化发生差异性改变。
DOI：
10.1016/j.ynstr.2020.100249
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发表时间：
2020-11
影响因子：
5
通讯作者：
Carola V
中科院分区：
文献类型：
--
作者：
Catale C;Bussone S;Lo Iacono L;Viscomi MT;Palacios D;Troisi A;Carola V
人们假设，经历的早期生活压力（ELS）事件的数量与儿童心理健康的改善之间存在比例关系。然而，不同类型的ELS经验可能与不同的神经心理生物学影响，由于压力的内在性质的差异。DNA甲基化是在成年期将ELS暴露“翻译”成神经生物学和行为异常的分子机制之一。在这里，我们研究了不同的ELS经历是否会对小鼠和人类大脑和血液样本中的整体DNA甲基化水平产生不同的影响。小鼠暴露于ELS会导致成年期出现可观察到的变化，与暴露于具有社会威胁的环境相比，暴露于社会隔离会导致多个大脑结构中的整体DNA甲基化水平发生更剧烈的变化。此外，这两种类型的压力对不同大脑区域和细胞群体（即小胶质细胞）的表观遗传编程产生了不同的影响。在一项初步临床研究中，对患有重度抑郁症或物质使用障碍的患者的血液总体DNA甲基化水平和儿童期忽视或虐待的暴露进行了研究。观察到心理健康诊断对全球甲基化水平的显着影响，但未检测到儿童虐待或忽视的影响。这些发现表明，不同类型的ELS通过特定大脑区域的DNA甲基化对表观遗传编程产生不同的影响，并且这些不同的影响与ELS经历后观察到的不同行为结果有关。
The existence of a proportional relationship between the number of early-life stress (ELS) events experienced and the impoverishment of child mental health has been hypothesized. However, different types of ELS experiences may be associated with different neuro-psycho-biological impacts, due to differences in the intrinsic nature of the stress. DNA methylation is one of the molecular mechanisms that have been implicated in the “translation” of ELS exposure into neurobiological and behavioral abnormalities during adulthood. Here, we investigated whether different ELS experiences resulted in differential impacts on global DNA methylation levels in the brain and blood samples from mice and humans. ELS exposure in mice resulted in observable changes in adulthood, with exposure to social isolation inducing more dramatic alterations in global DNA methylation levels in several brain structures compared with exposure to a social threatening environment. Moreover, these two types of stress resulted in differential impacts on the epigenetic programming of different brain regions and cellular populations, namely microglia. In a pilot clinical study, blood global DNA methylation levels and exposure to childhood neglect or abuse were investigated in patients presenting with major depressive disorder or substance use disorder. A significant effect of the mental health diagnosis on global methylation levels was observed, but no effect of either childhood abuse or neglect was detected. These findings demonstrate that different types of ELS have differential impacts on epigenetic programming, through DNA methylation in specific brain regions, and that these differential impacts are associated with the different behavioral outcomes observed after ELS experiences.
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DOI：
10.1017/s1461145713000394
发表时间：
2013-10-01
影响因子：
4.8
作者：
Anier, Kaili;Zharkovsky, Alexander;Kalda, Anti
通讯作者：
Kalda, Anti
影响因子：
4.8
作者：
Cecil, Charlotte A. M.;Viding, Essi;McCrory, Eamon J.
通讯作者：
McCrory, Eamon J.
影响因子：
15.1
作者：
Kinnally, Erin L.;Feinberg, Caroline;Kim, David;Ferguson, Kerel;Leibel, Rudolph;Coplan, Jeremy D.;Mann, J. John
通讯作者：
Mann, J. John
影响因子：
4.8
作者：
Bernstein, DP;Stein, JA;Zule, W
通讯作者：
Zule, W
影响因子：
4.8
作者：
Christ, Sharon L.;Kwak, Yoon Young;Lu, Ting
通讯作者：
Lu, Ting