Feb 24, 2009

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

Nature Neuroscience
Patrick O McGowanM J Meaney

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.

  • References50
  • Citations1126

References

  • References50
  • Citations1126

Citations

Mentioned in this Paper

EGR1 wt Allele
EGR1 gene
Protein Methylation
Autopsy
Transcription, Genetic
Neurons
Pituitary Diseases
Brain
Cytosine Methylation
Methylate

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