Stress is a major burden in many people's lives affecting their health and wellbeing. New research led by the University of Bristol has found that genes in the brain that play a crucial role in behavioural adaptation to stressful challenges are controlled by epigenetic mechanisms.
Adaptation to stress is known to require changes in the expression of so-called immediate-early genes in the brain, particularly in the hippocampus, a brain region that plays a crucial role in learning and memory.
Until now, however, the underlying molecular mechanisms controlling the expression of these genes has been unclear. Researchers revealed that stressful events result in epigenetic modifications within immediate-early genes in hippocampus neurons.
The epigenetic modification studied is DNA methylation, which acts to suppress expression of genes. The findings, published in the international journal Proceedings of National Academy of Sciences (PNAS), showed that stress results in DNA de-methylation in immediate-early genes thereby freeing the suppressed expression of these genes in the hippocampus and facilitating manifestation of adaptive behavioral responses.
The researchers found that the gene and behavioral responses to stress depended on the concentration of the compound SAM (s-adenosyl methionine). SAM is a so-called methyl donor, which is required by the enzyme that methylates DNA. When SAM levels were elevated, a subsequent stressful event did not result in DNA de-methylation but elicited enhanced DNA methylation of immediate early genes, which suppressed their expression and led to impaired behavioral adaptation.
Senior author, said: "We discovered in our studies a link between SAM, a compound produced by the liver, and stress-related responses in the brain, which is important to pursue in future research.
New insights into how the brain adapts to stress
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