Citation

McGowan PO, Sasaki A, D'Alessio AC, Dymov S, Labonté B, Szyf M, Turecki G, Meaney MJ. Nat. Neurosci. 2009; 12(3): 342-348.

Affiliation

Douglas Mental Health University Institute, 6875 LaSalle Boulevard, Montreal, Quebec, H4H 1R3, Canada.

Comment In:

Nat Neurosci 2009;12(3):241-3.

Copyright

(Copyright © 2009, Holtzbrinck Springer Nature Publishing Group)

DOI

10.1038/nn.2270

PMID

19234457

PMCID

PMC2944040

Abstract

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.

Language: en