The mechanism behind how stress impacts the brain, which details why some individuals are predisposed to depression when they experience chronic stress has been explained by researchers.
Researchers from Yamaguchi University in Japan have revealed complex molecular mechanisms associated with chronic stress.
"Many individuals exposed to stressful events do not show signs or symptoms of depression; however, some individuals exposed to psychological stress are predisposed to major depression," said senior study author, Dr. Yoshifumi Watanabe.
"Thus far, the molecular mechanisms underlying the susceptibility and adaptation to chronic stress within the brain are poorly understood," Watanabe said.
Watanabe and his colleagues used two genetically distinct mouse strains that exhibit different behavioral responses to chronic stress to look for genetic mechanisms associated with vulnerability to stressful events.
The researchers observed that, in contrast to the stress-resilient mice, the stress-vulnerable mice exhibited depression-like behaviors when exposed to chronic mild stress.
The stress-vulnerable mice had a lower level of gene expression for glial cell-derived neurotrophic factor (Gdnf). Neurotrophic factors are known to be important for regulation of brain plasticity and have been implicated in depression.
The reduced level of Gdnf expression was the result of DNA methylation and histone modifications. These changes, called epigenetic modifications, and the depressive behaviors were reversed by treatment of the stress-vulnerable mice with antidepressants.
"Dynamic epigenetic regulations of the Gdnf gene play important roles in determining both the susceptibility and the adaptation responses to chronic stressful events," said coauthor Shusaku Uchida.
The study was published by Cell Press in the January 27 issue of the journal Neuron.