Neuroscience
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The human brain has a remarkable capacity to adapt to and learn from a wide range of variations in the environment. However, environmental challenges can also precipitate psychiatric disorders in susceptible individuals. ⋯ Here we review how these two influences intersect at the epigenetic regulation of neuronal gene transcription, and we discuss how the regulation of genomic DNA methylation near key stress-response genes may influence psychological susceptibility or resilience to environmental stressors. Our goal is to offer a perspective on the epigenetics of stress responses that works to bridge the gap between the study of this molecular process in animal models and its potential usefulness for understanding stress vulnerabilities in humans.
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Childhood maltreatment (CM) has estimated prevalence among Western societies between 10% and 15%. As CM associates with increased risk of several psychiatric disorders, early age of illness onset, increased comorbidity and negative clinical outcome, it imposes a major public health, social and economic impact. Although the clinical consequences of CM are well characterized, a major challenge remains to understand how negative early-life events can affect brain function over extended periods of time. We review here both animal and human studies indicating that the epigenetic mechanism of DNA methylation is a crucial mediator of early-life experiences, thereby maintaining life-long neurobiological sequelae of CM, and strongly determining psychopathological risk.
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Chronic exposure to stress is associated with a number of psychiatric disorders, but little is known about the epigenetic mechanisms that underlie the stress response or resilience to chronic stress. We investigated histone acetylation in seven different brain regions of rats exposed to chronic social defeat stress: the dorsal hippocampus (dHPC), ventral hippocampus (vHPC), medial prefrontal cortex (mPFC), basolateral amygdala (BLA), locus coeruleus (LC), paraventricular thalamus (PVT), and dorsal raphe (DR) nucleus. This stress paradigm was unique in that it allowed rats to display resilience in the form of an active coping mechanism. ⋯ We assessed expression of histone modifying enzymes in the vHPC and the mPFC using quantitative real-time polymerase chain reaction (PCR) and found changes in expression of a number of targets. These included changes in Sirt1 and Sirt2 in the vHPC and changes in Kat5 in the mPFC. Overall, these results suggest that changes in histone acetylation and expression of histone modifying enzymes in these regions correlate with the behavioral response to stress in socially defeated rats.