Epigenetic influences on the developing brain: effects of hormones and nutrition

Abstract

The developing brain is subject to modifying influences, both in utero and early postnatally. Some of these are intrinsic, such as gonadal steroids, while others are externally imposed, such as maternal nutrition or stress. All of these variables can have enduring consequences by imposing epigenetic modifications on the genome that alter set points for activation in adulthood, thereby reflecting early-life programming. In this review, we provide an overview of the most well studied epigenetic processes that occur in the brain. Next, we summarize the studies to date that have implicated gonadal steroids, stress exposure, and nutritional deficits/excess in changes in neural epigenetic marks, which ultimately alter brain development, but we also note that this field is still in its infancy. Epigenetic regulators include DNA methylation, changes to the chromatin via acetylation and other chemical modifiers, and noncoding RNAs all of which impact the expression of specific genes. In this way gonadal steroids in the developing male fetus direct masculinization of adult brain and behavior, and similarly in utero exposure to a high-fat or calorie-restricted diet impacts glucose metabolism and body fat composition throughout life. Stress early in life changes the sensitivity of the hypothalamic-pituitary-adrenal (HPA) axis to subsequent stressors and this too is mediated, at least in part, by epigenetic changes to key genes to alter the responsiveness threshold. Epigenetics is the integration of the environment and the genome, and hormones and nutrition provide the bridge that allows that integration to occur. [ABSTRACT FROM AUTHOR]