Epigenetic effects of stress and corticosteroids in the brain

Abstract

Stress is a common life event with potentially long lasting effects on health and behavior. Stress, and the corticosteroid hormones that mediate many of its effects, are well known for their ability to alter brain function and plasticity. While genetic susceptibility may influence the impact of stress on the brain, it does not provide us with a complete understanding of the capacity of stress to produce long lasting perturbations on the brain and behavior. The growing science of epigenetics, however, shows great promise of deepening our understanding of the persistent impacts of stress and corticosteroids on health and disease. Epigenetics, broadly defined, refers to influences on phenotype operating above the level of the genetic code itself. At the molecular level, epigenetic events belong to three major classes: DNA methylation, covalent histone modification and non-coding RNA. This review will examine the bi-directional interactions between stress and corticosteroids and epigenetic mechanisms in the brain and how the novel insights, gleaned from recent research in neuro-epigenetics, change our understanding of mammalian brain function and human disease states.

Keywords: brain development; corticosteroids; epigenetics; glucocorticoid receptor; stress.

Figure 1

Figure one is a representation of the effects of stress on the three main epigenetic mechanisms as presently understood. Stress may act to alter modifications (green) of the tails (red) of the core histone proteins of the nucleosome (yellow). Some modifications, such as acetylation, or histone 3K4 trimethylation, are associated with a loose, euchromatic state and active gene transcription. Others, such as Histone H3K9 or K27 trimethylation, are associated with dense heterochromatin and gene silencing or repressed transcription. DNA methylation (purple) is commonly associated with transcriptional repression, the function of more exotic DNA modifications, such as cytosine hydroxymethylation is a subject of intense interest, but as yet unresolved. Non-coding RNA species (orange), such as microRNAs, may alter gene transcription as well, but have effects post-transcriptionally on both mRNA stability and translation into protein.