Epigenetic influence of stress and the social environment

Abstract

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.

Keywords: DNA methylation; epigenetic; histone modification; maternal; rodent; stress; transgenerational.

Figure 1

Illustration of the processes of DNA methylation and histone modification. (A) DNA methylation is a process in which methyl chemicals (Me) are added to cytosines in the DNA sequence by the enzyme DNA methyltransferases (DNMTs). Methylated DNA is highly compact, and DNA methylation typically leads to reduced gene expression or gene silencing. (B) The addition of an acetyl chemical (Ac) to histone proteins can loosen the interactions between histones and DNA and increase the level of gene transcription (top). In contrast, deacetylated histones cluster closely to the DNA and suppress gene expression (bottom). mRNA, messenger RNA.