Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse.

TitleEpigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse.
Publication TypeJournal Article
AuthorsMcGowan, Patrick O., Aya Sasaki, Ana C. D'Alessio, Sergiy Dymov, Benoit Labonté, Moshe Szyf, Gustavo Turecki, and Michael J. Meaney
PubMed ID19234457
PubMed Central IDPMC2944040
Grant ListR01 HD051897-04 / HD / NICHD NIH HHS / United States

Maternal care influences hypothalamic-pituitary-adrenal (HPA) function in the rat through epigenetic programming of glucocorticoid receptor expression. In humans, childhood abuse alters HPA stress responses and increases the risk of suicide. We examined epigenetic differences in a neuron-specific glucocorticoid receptor (NR3C1) promoter between postmortem hippocampus obtained from suicide victims with a history of childhood abuse and those from either suicide victims with no childhood abuse or controls. We found decreased levels of glucocorticoid receptor mRNA, as well as mRNA transcripts bearing the glucocorticoid receptor 1F splice variant and increased cytosine methylation of an NR3C1 promoter. Patch-methylated NR3C1 promoter constructs that mimicked the methylation state in samples from abused suicide victims showed decreased NGFI-A transcription factor binding and NGFI-A-inducible gene transcription. These findings translate previous results from rat to humans and suggest a common effect of parental care on the epigenetic regulation of hippocampal glucocorticoid receptor expression.

Title Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse.
Publication Title Nat Neurosci
Publication Type Journal Article
Published Year 2009
Authors P.O. McGowan; A. Sasaki; A.C. D'Alessio; S. Dymov; B. Labonté; M. Szyf; G. Turecki; M.J. Meaney
ISSN Number 1546-1726
PubMed ID 19234457
PubMed Central ID PMC2944040
Grant List
R01 HD051897-04 HD NICHD NIH HHS United States

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