Epigenetic mechanisms underlying stress-induced depression

Abstract

Stressful life events are a major contributor to the development of major depressive disorder. Environmental perturbations like stress change gene expression in the brain, leading to altered behavior. Gene expression is ultimately regulated by chromatin structure and the epigenetic modifications of DNA and the histone proteins that make up chromatin. Studies over the past two decades have demonstrated that stress alters the epigenetic landscape in several brain regions relevant for depressive-like behavior in rodents. This chapter will discuss epigenetic mechanisms of brain histone acetylation, histone methylation, and DNA methylation that contribute to adult stress-induced depressive-like behavior in rodents. Several biological themes have emerged from the examination of the brain transcriptome after stress such as alterations in the neuroimmune response, neurotrophic factors, and synaptic structure. The epigenetic mechanisms regulating these processes will be highlighted. Finally, pharmacological and genetic manipulations of epigenetic enzymes in rodent models of depression will be discussed as these approaches have demonstrated the ability to reverse stress-induced depressive-like behaviors and provide proof-of-concept as novel avenues for the treatment of clinical depression.

Keywords: DNA methylation; DNMT; Depression; Epigenetic; HDAC; Histone acetylation; Histone methylation; Sirtuin; Stress; TET.