Japanese Journal of Biological Psychiatry
Online ISSN : 2186-6465
Print ISSN : 2186-6619
Epigenetic regulation in depression
Koji OtsukiShusaku UchidaTeruyuki HobaraYoshifumi Watanabe
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Keywords: GDNF, HDAC

2011 Volume 22 Issue 2 Pages 89-95


Recent research has raised the notion that epigenetic mechanisms (e.g., DNA methylation and histone modifications), which exert lasting control over gene expression without altering the genetic code, could mediate stable changes in brain function. However, the role of environmental factors along with genetic factors in the epigenetic regulation of the pathogenesis of depression is largely unknown. Two genetically distinct mice strains that exhibit different behavioral responses to chronic stress were used to demonstrate how the differential epigenetic status of glial cell- derived neurotrophic factor (GDNF) gene in the ventral striatum modulates susceptibility and adaptation to chronic stress. Our results indicate crucial roles of histone modifications and DNA methylation by histone deacetylase2 (HDAC2) and MeCP2 for the control of GDNF expression and subsequent behavioral responses to chronic stress. In addition, we also investigated the effect of antidepressants on the epigenetic regulation of GDNF expression. We found that the antidepressants enhance the induction of GDNF transcription by the increased histone acetylation of GDNF gene promoter. Furthermore, HDAC4 inhibited the induction of GDNF by antidepressant. Finally, we investigated whether the expressions of GDNF and epigenetic- related molecules would be altered in mood disorder patients. We found the aberrant expression of GDNF, HDAC2, HDAC4 in mood disorder patients. Thus, our data provide novel insights, suggesting that epigenetic mechanisms of GDNF contribute to pathogenesis or pathophysiology of depression.

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© 2011 Japanese Society of Biological Psychiatry
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