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Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse.
- Source :
-
Nature neuroscience [Nat Neurosci] 2009 Mar; Vol. 12 (3), pp. 342-8. - Publication Year :
- 2009
-
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.
- Subjects :
- Adult
Base Sequence
Cell Line
DNA Methylation genetics
Female
Hippocampus pathology
Humans
Male
Middle Aged
Molecular Sequence Data
Promoter Regions, Genetic physiology
Receptors, Glucocorticoid biosynthesis
Receptors, Glucocorticoid physiology
Suicide psychology
Young Adult
Adult Survivors of Child Abuse psychology
Epigenesis, Genetic physiology
Hippocampus physiology
Receptors, Glucocorticoid genetics
Receptors, Glucocorticoid metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1546-1726
- Volume :
- 12
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Nature neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 19234457
- Full Text :
- https://doi.org/10.1038/nn.2270