Anatomy of hippocampal circuit into which new neurons integrate. Neurogenesis is localized to the dentate gyrus (DG) region, where only excitatory granule cells are continually produced throughout life. The DG has a complex local circuitry, with both inhibitory interneurons and excitatory feedback neurons (mossy cells) participating in the network’s behavior. Granule cells in the DG project to the CA3 region, which in addition to a robust recurrent connection then projects to the CA1 region. The CA1 then projects back to the entorhinal cortex and subiculum regions, closing the “hippocampal loop.”
Stressful events result in epigenetic modifications within immediate-early genes in hippocampus neurons. The findings showed that stress results in DNA demethylation in immediate-early genes thereby freeing the suppressed expression of these genes in the hippocampus and facilitating manifestation of adaptive behavioural responses.
The gene and behavioural 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 behavioural adaptation.
Hans Reul, Professor of Neuroscience of Bristol’s School of Clinical Sciences, 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.
“Stress-related psychiatric disorders like major depression, anxiety and post-traumatic stress disorders are presently among the most debilitating illnesses known to man. Prevention of the detrimental effects of stress is thought to depend on effective coping and long-lasting adaptive behavioural responses.”
According to the scientists, this new research could lead to the development of novel pharmacological and other therapeutic interventions that promote appropriate behavioural responses to stress and help in the treatment of stress-evoked psychiatric disorders. http://www.bristol.ac.uk/news/2016/april/brain-adapts-to-stress.html
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