Abstract
Consolidation of contextual memories after a stressful encounter is essential for the survival of an organism and in allowing a more appropriate response to be elicited should the perceived threat reoccur. Recent evidence has explored the complex role that epigenetic mechanisms play in the formation of such memories, and the underlying signaling pathways are becoming more apparent. The glucocorticoid receptor (GR) has been shown to play a key role in these events having both genomic and non-genomic actions in the brain. GR has been shown to interact with the extracellular signal-regulated kinase mitogen-activated protein kinase (ERK MAPK) signaling pathway which, in concert, drives epigenetic modifications and chromatin remodeling, resulting in gene induction and memory consolidation. Evidence indicates that stressful events can have an effect on the offspring in utero, and that epigenetic marks altered early in life may persist into adulthood. A new and controversial area of research, however, suggests that epigenetic modifications could be inherited through the germline, a concept known as transgenerational epigenetics. This review explores the role that epigenetic processes play in the central nervous system, specifically in the consolidation of stress-induced memories, the concept of transgenerational epigenetic inheritance, and the potential role of epigenetics in revolutionizing the treatment of stress-related disorders through the emerging field of pharmacoepigenetics and personalized medical treatment.
Highlights
The stress response is initiated when an animal encounters a perceived harmful event or situation, physical and/or psychological, that threatens to disrupt homeostasis and requires appropriate physiological and behavioral responses in order to cope with the stressor [1,2]
We found that forced swimming results in increased DNA methylation of the Nr3c1 gene associated with an enhanced binding of DNA methyltransferase 3A (DNMT3A), which may explain the reduction in gene expression after stress
The process of consolidating stress-related memories involves a number of complex pathways such as the concomitant activation of NMDA-Rs and glucocorticoid receptor (GR) resulting in the activation of the ERK MAPK pathway, and subsequent epigenetic modifications and gene transcriptional responses
Summary
The stress response is initiated when an animal encounters a perceived harmful event or situation, physical and/or psychological, that threatens to disrupt homeostasis and requires appropriate physiological and behavioral responses in order to cope with the stressor [1,2]. A psychological stressor requires the animal to assess the situation and make a decision through cognitive evaluations. These stressors evoke neurobiological changes, which result in behavioral adaption to increase the animal’s chance of survival [3,4]. We know that cells all contain the same genetic information they display a rich variety of phenotypes, varying greatly in morphology and function This is recognized as the origin of the differential expression of genes that occurs without changes to the DNA sequence. This review will explore the role of epigenetic and molecular mechanisms in the central nervous system (CNS) covering current mechanisms underpinning stress-related learning and memory, transgenerational epigenetics, the role epigenetics plays in neuropsychiatric disorders, and the potential of using epigenetic modifications as biomarkers, or to inform the most effective course of treatment
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