Epigenetics of Stress Adaptations in the Brain.

Department of Animal Behavior, Institute of Genetics and Animal Breeding, Polish Academy of Sciences, Postepu 1, 05-552 Jastrzebiec n/Warsaw, Poland. Electronic address: .
Brain research bulletin (Impact Factor: 2.72). 07/2013; 98. DOI: 10.1016/j.brainresbull.2013.07.003
Source: PubMed


Recent findings in epigenetics shed new light on the regulation of gene expression in the central nervous system (CNS) during stress. The most frequently studied epigenetic mechanisms are DNA methylation, histone modifications and microRNA activity. These mechanisms stably determine cell phenotype but can also be responsible for dynamic molecular adaptations of the CNS to stressors. The limbic-hypothalamic-pituitary-adrenal axis (LHPA) is the primary circuit that initiates, regulates and terminates a stress response. The same brain areas that control stress also react to stress dynamically and with long-term consequences. One of the biological processes evoking potent adaptive changes in the CNS such as changes in behavior, gene activity or synaptic plasticity in the hippocampus is psychogenic stress. This review summarizes the current data regarding the epigenetic basis of molecular adaptations in the brain including genome-wide epigenetic changes of DNA methylation and particular genes involved in epigenetic responses that participate in the brain response to chronic psychogenic stressors. It is concluded that specific epigenetic mechanisms in the CNS are involved in the stress response.

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    • "From a molecular point of view, recent data have indicated the participation of several genes in the adaptive response to stress, including Bdnf (brain-derived neurotrophic factor), which is involved in neuronal plasticity [8], and Dnmt1 (DNA methyltransferase 1), which plays a general role in maintaining DNA methylation [9]. The participation of epigenetic changes in molecular adaptive responses to behavioral stress have been strongly supported by recent evidence [10] [11], however, despite the rapidly expanding knowledge in this field little is known about the contribution of http://dx.doi. "
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    • "One mechanism whereby HPA axis sensitization is likely to occur is through epigenetic regulation of stress response processes (21, 27). Evidence shows that exposure to various forms of stress result in multiple epigenetic changes in limbic regions as well as the HPA axis (21, 27). Interestingly, a recent study by Klendel and colleagues (18) found that only individuals who exhibited allele-specific DNA demethylation in functional glucocorticoid response elements of FK506 binding protein 5 (FKBP5), were prone to developing persistent cortisol dysregulation (18, 21). "
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    • "Gene expression is controlled by transcription factors and epigenetic regulators: DNA methylation/demethylation and histone modifications such as methylation/demethylation, acetylation/deacetylation, and phosphorylation/dephosphorylation, which regulate access of transcription factors and RNA polymerase II to gene promoters. Aberrant DNA methylation and histone modifications are involved in diverse neuronal functions and neurological disorders such as synaptic plasticity and memory formation (Sultan and Day, 2011), Alzheimer, Parkinson, and Huntington diseases (Gebicke-Haerter, 2012; Gray, 2011; Zawia et al., 2009), schizophrenia (Harrison and Dexter, 2013), epilepsy (Hwang et al., 2013), acute and chronic stress (Stankiewicz et al., 2013), and stroke (Hwang et al., 2013). However, there are very few direct data on the involvement of epigenetic processes in neurodegeneration (Chestnut et al., 2011). "
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