Mice subjected to stress caused by the presence of an aggressive intruder, repress the gene that produces a growth factor called brain derived neurotrophic factor (BDNF), reports a paper in the March 2006 issue of Nature Neuroscience. This finding suggests a molecular pathway by which stress may cause lasting changes in gene regulation.
Eric Nestler and colleagues have previously reported that such socially stressed mice show a form of depression that mimics the human condition, and that treatment with antidepressants can improve their behavior. The team now uses this model to study gene changes that take place when mice are exposed to chronic defeat stress and when they are treated with antidepressants. These changes last for over a month after the social stress ends and are mediated by an increase in histone methylation -- which usually represses gene expression -- at the Bdnf promoter sites, leading to more stable repression of the gene. Treatment with the antidepressant imipramine increased histone acetylation -- which usually promotes gene expression -- by repressing an enzyme that deacetylates histones, thus reversing the effect on the Bdnf promoter.
If similar changes occur in humans, which is yet to be demonstrated, this work may lead to new therapeutic targets for stress-induced depression.
Eric Nestler (University of Texas Southwestern Medical Center, TX, USA)
Additional contact for comment on paper:
Steven Hyman (Harvard Medical School, MA, USA)
Abstract available online.
(C) Nature Neuroscience press release.
Message posted by: Trevor M. D'Souza