Gudsnuk Kathryn, Champagne Frances A
Department of Psychology, Columbia University, New York, NY 10027, USA.
ILAR J. 2012;53(3-4):279-88. doi: 10.1093/ilar.53.3-4.279.
Animal models of early-life stress and variation in social experience across the lifespan have contributed significantly to our understanding of the environmental regulation of the developing brain. Plasticity in neurobiological pathways regulating stress responsivity, cognition, and reproductive behavior is apparent during the prenatal period and continues into adulthood, suggesting a lifelong sensitivity to environmental cues. Recent evidence suggests that dynamic epigenetic changes--molecular modifications that alter gene expression without altering the underlying DNA sequence--account for this plasticity. In this review, we highlight studies of laboratory rodents that illustrate the association between the experience of prenatal stress, maternal separation, maternal care, abusive caregiving in infancy, juvenile social housing, and adult social stress and variation in DNA methylation and histone modification. Moreover, we discuss emerging evidence for the transgenerational impact of these experiences. These experimental paradigms have yielded insights into the potential role of epigenetic mechanisms in mediating the effects of the environment on human development and also indicate that consideration of the sensitivity of laboratory animals to environmental cues may be an important factor in predicting long-term health and welfare.
生命早期应激的动物模型以及整个生命周期中社会经历的变化,对我们理解发育中大脑的环境调节起到了重要作用。调节应激反应、认知和生殖行为的神经生物学通路的可塑性在孕期就很明显,并持续到成年期,这表明对环境线索具有终身敏感性。最近的证据表明,动态表观遗传变化——即不改变潜在DNA序列而改变基因表达的分子修饰——是这种可塑性的原因。在这篇综述中,我们重点介绍了对实验啮齿动物的研究,这些研究阐明了产前应激、母婴分离、母性照料、婴儿期虐待性照料、幼年群居以及成年社会应激等经历与DNA甲基化和组蛋白修饰变化之间的关联。此外,我们还讨论了这些经历产生跨代影响的新证据。这些实验范式为表观遗传机制在介导环境对人类发育影响方面的潜在作用提供了见解,同时也表明考虑实验动物对环境线索的敏感性可能是预测长期健康和福祉的一个重要因素。