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早期生活逆境的表观遗传学:当前的局限性和可能的解决方案。

The Epigenetics of Early Life Adversity: Current Limitations and Possible Solutions.

机构信息

Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada.

Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada; McGill University, Montreal, QC, Canada.

出版信息

Prog Mol Biol Transl Sci. 2018;157:343-425. doi: 10.1016/bs.pmbts.2018.01.008. Epub 2018 Mar 30.

Abstract

Adverse experiences during sensitive postnatal developmental periods can disrupt the calibration of fundamental systems and increase the risk of a wide range of adult disease states, including psychiatric illnesses. Accumulating evidence suggests that epigenetic modifications involving DNA methylation, posttranslational histone modifications, and noncoding RNAs may be a key mediating factor in this disruption. Accumulating evidence from both animal models and human studies suggests that early life adversity alters the epigenome at multiple loci across the genome, but that the specific alterations, and the associated transcriptomic and psychiatric outcomes may be dependent on multiple individual factors. Here we will review the current findings on early life adversity associated alterations of the epigenome in animal models and humans, discuss current limitations, and highlight possible solutions and future directions.

摘要

在敏感的产后发育期经历不良体验可能会破坏基本系统的校准,并增加广泛的成年疾病状态的风险,包括精神疾病。越来越多的证据表明,涉及 DNA 甲基化、翻译后组蛋白修饰和非编码 RNA 的表观遗传修饰可能是这种破坏的关键介导因素。动物模型和人类研究的积累证据表明,早期生活逆境会改变基因组中多个位置的表观基因组,但特定的改变以及相关的转录组和精神疾病结果可能取决于多个个体因素。在这里,我们将回顾动物模型和人类中与早期生活逆境相关的表观基因组改变的现有发现,讨论当前的局限性,并强调可能的解决方案和未来方向。

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