Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action - PubMed (original) (raw)

doi: 10.1038/nn1659. Epub 2006 Feb 26.

Affiliations

PMID: 16501568
DOI: 10.1038/nn1659

Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action

Nadia M Tsankova et al. Nat Neurosci. 2006 Apr.

Abstract

To better understand the molecular mechanisms of depression and antidepressant action, we administered chronic social defeat stress followed by chronic imipramine (a tricyclic antidepressant) to mice and studied adaptations at the levels of gene expression and chromatin remodeling of five brain-derived neurotrophic factor (Bdnf) splice variant mRNAs (I-V) and their unique promoters in the hippocampus. Defeat stress induced lasting downregulation of Bdnf transcripts III and IV and robustly increased repressive histone methylation at their corresponding promoters. Chronic imipramine reversed this downregulation and increased histone acetylation at these promoters. This hyperacetylation by chronic imipramine was associated with a selective downregulation of histone deacetylase (Hdac) 5. Furthermore, viral-mediated HDAC5 overexpression in the hippocampus blocked imipramine's ability to reverse depression-like behavior. These experiments underscore an important role for histone remodeling in the pathophysiology and treatment of depression and highlight the therapeutic potential for histone methylation and deacetylation inhibitors in depression.

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Comment in

Even chromatin gets the blues.
Hyman SE. Hyman SE. Nat Neurosci. 2006 Apr;9(4):465-6. doi: 10.1038/nn0406-465. Nat Neurosci. 2006. PMID: 16568101 No abstract available.

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Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action - PubMed (original) (raw)