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早期生活经历、表观遗传学与发育中的大脑。

Early-life experience, epigenetics, and the developing brain.

作者信息

Kundakovic Marija, Champagne Frances A

机构信息

Department of Psychology, Columbia University, New York, NY, USA.

出版信息

Neuropsychopharmacology. 2015 Jan;40(1):141-53. doi: 10.1038/npp.2014.140. Epub 2014 Jun 11.

Abstract

Development is a dynamic process that involves interplay between genes and the environment. In mammals, the quality of the postnatal environment is shaped by parent-offspring interactions that promote growth and survival and can lead to divergent developmental trajectories with implications for later-life neurobiological and behavioral characteristics. Emerging evidence suggests that epigenetic factors (ie, DNA methylation, posttranslational histone modifications, and small non-coding RNAs) may have a critical role in these parental care effects. Although this evidence is drawn primarily from rodent studies, there is increasing support for these effects in humans. Through these molecular mechanisms, variation in risk of psychopathology may emerge, particularly as a consequence of early-life neglect and abuse. Here we will highlight evidence of dynamic epigenetic changes in the developing brain in response to variation in the quality of postnatal parent-offspring interactions. The recruitment of epigenetic pathways for the biological embedding of early-life experience may also have transgenerational consequences and we will describe and contrast two routes through which this transmission can occur: experience dependent vs germline inheritance. Finally, we will speculate regarding the future directions of epigenetic research and how it can help us gain a better understanding of the developmental origins of psychiatric dysfunction.

摘要

发育是一个动态过程,涉及基因与环境之间的相互作用。在哺乳动物中,产后环境的质量由亲代与子代之间的相互作用塑造,这些相互作用促进生长和生存,并可能导致不同的发育轨迹,对后期的神经生物学和行为特征产生影响。新出现的证据表明,表观遗传因素(即DNA甲基化、翻译后组蛋白修饰和小非编码RNA)可能在这些亲代抚育效应中起关键作用。尽管这些证据主要来自啮齿动物研究,但在人类中对这些效应的支持也越来越多。通过这些分子机制,精神病理学风险的差异可能会出现,特别是由于早期生活中的忽视和虐待。在这里,我们将强调发育中的大脑中动态表观遗传变化的证据,这些变化是对产后亲代与子代相互作用质量变化的反应。表观遗传途径参与早期生活经历的生物学嵌入可能也会产生跨代后果,我们将描述和对比这种传递可能发生的两种途径:经验依赖型与种系遗传。最后,我们将推测表观遗传学研究的未来方向,以及它如何帮助我们更好地理解精神功能障碍的发育起源。

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