Epigenetics of stress

Poor stress-coping is associated with a greater chance of developing a psychiatric illness such as post-traumatic stress disorder (PTSD) or depression. Lifestyle interventions which facilitate more appropriate responses to stress are much sought after. Exercise is one such intervention and is now commonly being prescribed as a cotreatment along with drugs for treating depression. Exercised rodents display reduced anxiety and impulsivity in a variety of behavioral paradigms. Rats exposed to psychological stress show differential epigenetic and gene expression mechanisms at the dentate gyrus (DG) after long-term voluntary exercise. Alterations within ERK MAPK signalling to chromatin seem to modulate the number of epigenetically marked neurons in the DG, improving cognitive responses to a stress-related event. Other lifestyle interventions such as nutrition or better maternal care in early life have been shown to induce changes at the epigenome which impact positively on mental health

Epigenetic mechanisms in stress and adaptation

Epigenetic mechanisms are processes at the level of the chromatin that control the expression of genes but their role in neuro-immuno-endocrine communication is poorly understood. This review focuses on epigenetic modifications induced by a range of stressors, both physical and psychological, and examines how these variations can affect the biological activity of cells. It is clear that epigenetic modifications are critical in explaining how environmental factors, which have no effect on the DNA sequence, can have such profound, long-lasting influences on both physiology and behavior. A signaling pathway involving activation of MEK-ERK1/2, MSK1, and Elk-1 signaling molecules has been identified in the hippocampus which results in the phospho-acetylation of histone H3 and modification of gene expression including up-regulation of immediate early genes such as c-Fos. This pathway can be induced by a range of challenging experiences including forced swimming, Morris water maze learning, fear conditioning and exposure to the radial maze. Glucocorticoid (GC) hormones, released as part of the stress response and acting via glucocorticoid receptors (GRs), enhance signaling through the ERK1/2/MSK1–Elk-1 pathway and thereby increase the impact on epigenetic and gene expression mechanisms. The role of synergetic interactions between these pathways in adaptive responses to stress and learning and memory paradigms is discussed, in addition we speculate on their potential role in immune function

Stress, epigenetic control of gene expression and memory formation

Making memories of a stressful life event is essential for an organism's survival as it allows it to adapt and respond in a more appropriate manner should the situation occur again. However, it may be envisaged that extremely stressful events can lead to formation of traumatic memories that are detrimental to the organism and lead to psychiatric disorders such as post-traumatic stress disorder (PTSD). The neurotransmitter glutamate and the ERK MAPK signaling pathway play a principal role in learning and memory. Glucocorticoid hormones acting via the glucocorticoid receptor have been shown to strengthen the consolidation of memories of stressful events. The ERK MAPK signaling pathway and glucocorticoid receptor-mediated actions have recently been shown to drive epigenetic modifications and conformational changes in the chromatin, stimulating the expression of neuroplasticity-related genes involved in stress-related learning and memory processes. The main epigenetic regulatory mechanisms are histone modifications and DNA (de-)methylation. Recently, studies have demonstrated that these processes are acting together in concert to regulate gene expression required for memory consolidation.\ud \ud This review explores the role of stress in learning and memory paradigms and the participating signaling pathways and epigenetic mechanisms and the enzymes that control these modifications during the consolidation process of memory formation