Article abstract


Nature Neuroscience 12, 342 - 348 (2009)
Published online: 22 February 2009 | doi:10.1038/nn.2270

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

Patrick O McGowan1,2, Aya Sasaki1,2, Ana C D'Alessio3, Sergiy Dymov3, Benoit Labonté1,4, Moshe Szyf2,3, Gustavo Turecki1,4 & Michael J Meaney1,2,5


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.

Top
  1. Douglas Mental Health University Institute, 6875 LaSalle Boulevard, Montreal, Quebec, H4H 1R3, Canada.
  2. Sackler Program for Epigenetics & Developmental Psychobiology, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec, H3G 1Y6, Canada.
  3. Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec, H3G 1Y6, Canada.
  4. McGill Group for Suicide Studies, 6875 LaSalle Boulevard, Douglas Mental Health University Institute, Montreal, Quebec, H4H 1R3, Canada.
  5. Singapore Institute for Clinical Sciences, Brenner Centre for Molecular Medicine, 30 Medical Drive, Singapore 117609.

Correspondence to: Michael J Meaney1,2,5 e-mail: michael.meaney@mcgill.ca

Correspondence to: Gustavo Turecki1,4 e-mail: gustavo.turecki@mcgill.ca

Correspondence to: Moshe Szyf2,3 e-mail: moshe.szyf@mcgill.ca



MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated.

REVIEWS

IBS: an epigenetic perspective

Nature Reviews Gastroenterology & Hepatology Perspective (01 Aug 2010)

See all 20 matches for Reviews

NEWS AND VIEWS

How adversity gets under the skin

Nature Neuroscience News and Views (01 Mar 2009)

Mothering style and methylation

Nature Neuroscience News and Views (01 Aug 2004)