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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Available from: Adrian Stankiewicz
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    • "Rybnikova). Rudenko and Tsai, 2014; Stankiewicz et al., 2013). Epigenetic modifications are carried out by attaching specific chemical groups both to the bases of DNA (DNA methylation) or to the amino acid residues at the N-terminal tails of nucleosome histones (acetylation , phosphorylation, methylation, ubiquitylation, sumoylation, etc.) and cause changes in chromatin structure (Bannister and Kouzarides, 2011). "
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    ABSTRACT: Acetylation of nucleosome histones results in relaxation of DNA and its availability for the transcriptional regulators, and is generally associated with the enhancement of gene expression. Although it is well known that activation of a variety of pro-adaptive genes represents a key event in the development of brain hypoxic/ischemic tolerance, the role of epigenetic mechanisms, in particular histone acetylation, in this process is still unexplored. The aim of the present study was to investigate changes in acetylation of histones in vulnerable brain neurons using original well-standardized model of hypobaric hypoxia and preconditioning-induced tolerance of the brain. Using quantitative immunohistochemistry and Western blot, effects of severe injurious hypobaric hypoxia (SH, 180mm Hg, 3h) and neuroprotective preconditioning mode (three episodes of 360mm Hg for 2h spaced at 24h) on the levels of the acetylated proteins and acetylated H3 Lys24 (H3K24ac) in the neocortex and hippocampus of rats were studied. SH caused global repression of the acetylation processes in the neocortex (layers II-III, V) and hippocampus (CA1, CA3) by 3-24h, and this effect was prevented by the preconditioning. Moreover, hypoxic preconditioning remarkably increased the acetylation of H3K24 in response to SH in the brain areas examined. The preconditioning hypoxia without subsequent SH also stimulated acetylation processes in the neocortex and hippocampus. The moderately enhanced expression of the acetylated proteins in the preconditioned rats was maintained for 24h, whereas acetylation of H3K24 was intense but transient, peaked at 3h. The novel data obtained in the present study indicate that large activation of the acetylation processes, in particular acetylation of histones might be essential for the development of brain hypoxic tolerance.
    Full-text · Article · Nov 2015 · Acta histochemica
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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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    ABSTRACT: The vulnerability of epigenetic marks of brain cells to environmental stimuli and its implication for health have been recently debated. Thus, we used the rat model of acute restraint stress (ARS) to evaluate the impact of stress on the global DNA methylation and on the expression of the Dnmt1 and Bdnf genes of hippocampus, cortex, hypothalamus and periaqueductal gray (PAG). Furthermore, we verified the potential of physical exercise to modulate epigenetic responses evoked by ARS. Sedentary male Wistar rats were submitted to ARS at the 75th postnatal day (PND), whereas animals from a physically active group were previously submitted to swimming sessions (35–74th PND) and to ARS at the 75th PND. Global DNA methylation profile was quantified using an ELISA-based method and the quantitative expression of the Dnmt1 and Bdnf genes was evaluated by real-time PCR. ARS induced a decrease in global DNA methylation in hippocampus, cortex and PAG of sedentary animals and an increased expression of Bdnf in PAG. No change in DNA methylation was associated with ARS in the exercised animals, although it was associated with abnormal expression of Dnmt1 and Bdnf in cortex, hypothalamus and PAG. Our data reveal that ARS evokes adaptive changes in global DNA methylation of rat brain that are independent of the expression of the Dnmt1 gene but might be linked to abnormal expression of the Bdnf gene in the PAG. Furthermore, our evidence indicates that physical exercise has the potential to modulate changes in DNA methylation and gene expression consequent to ARS.
    Full-text · Article · Nov 2014 · Behavioural Brain Research
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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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    ABSTRACT: The mood disorder prodrome is conceptualized as a symptomatic, but not yet clinically diagnosable stage of an affective disorder. Although a growing area, more focused research is needed in the pediatric population to better characterize psychopathological symptoms and biological markers that can reliably identify this very early stage in the evolution of mood disorder pathology. Such information will facilitate early prevention and intervention, which has the potential to affect a person's disease course. This review focuses on the prodromal characteristics, risk factors, and neurobiological mechanisms of mood disorders. In particular, we consider the influence of early-life stress, inflammation, and allostatic load in mediating neural mechanisms of neuroprogression. These inherently modifiable factors have known neuroadaptive and neurodegenerative implications, and consequently may provide useful biomarker targets. Identification of these factors early in the course of the disease will accordingly allow for the introduction of early interventions which augment an individual's capacity for psychological resilience through maintenance of synaptic integrity and cellular resilience. A targeted and complementary approach to boosting both psychological and physiological resilience simultaneously during the prodromal stage of mood disorder pathology has the greatest promise for optimizing the neurodevelopmental potential of those individuals at risk of disabling mood disorders.
    Full-text · Article · Apr 2014 · Frontiers in Psychiatry
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