Epigenetic Mechanisms for the Early Environmental Regulation of Hippocampal Glucocorticoid Receptor Gene Expression in Rodents and Humans

Parental care influences development across mammals. In humans such influences include effects on phenotypes, such as stress reactivity, which determine individual differences in the vulnerability for affective disorders. Thus, the adult offspring of rat mothers that show an increased frequency of p...

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Published in:Neuropsychopharmacology (New York, N.Y.) Vol. 38; no. 1; pp. 111 - 123
Main Authors: Zhang, Tie Yuan, Labonté, Benoit, Wen, Xiang Lan, Turecki, Gustavo, Meaney, Michael J
Format: Journal Article
Language:English
Published: England Nature Publishing Group 01.01.2013
Subjects:
Affective disorders
Animals
Behavior
Child abuse & neglect
Children
Clinical outcomes
Development
DNA methylation
Environmental regulations
Epigenesis, Genetic - physiology
Epigenetics
Families & family life
Gene expression
Gene Expression Regulation
Genomes
Glucocorticoid receptors
Grooming
Hippocampus
Hippocampus - physiology
Histones
Humans
Hypothalamic-pituitary-adrenal axis
Influence
Intracellular signalling
Maternal Behavior - physiology
Maternal Behavior - psychology
Mental depression
Mental disorders
Mental health
Neuropsychopharmacology Reviews
Post-translation
Progeny
Promoters
Rats
Receptors, Glucocorticoid - biosynthesis
Receptors, Glucocorticoid - genetics
Reviews
Sex crimes
Sexual abuse
Social Environment
Stress
Canada
Singapore
ISSN:0893-133X, 1740-634X, 1740-634X
Online Access:Get full text
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Summary:Parental care influences development across mammals. In humans such influences include effects on phenotypes, such as stress reactivity, which determine individual differences in the vulnerability for affective disorders. Thus, the adult offspring of rat mothers that show an increased frequency of pup licking/grooming (ie, high LG mothers) show increased hippocampal glucocorticoid receptor (GR) expression and more modest hypothalamic-pituitary-adrenal responses to stress compared with the offspring of low LG mothers. In humans, childhood maltreatment associates decreased hippocampal GR expression and increased stress responses in adulthood. We review the evidence suggesting that such effects are mediated by epigenetic mechanisms, including DNA methylation and hydroxymethylation across GR promoter regions. We also present new findings revealing associated histone post-translational modifications of a critical GR promoter in rat hippocampus. Taken together these existing evidences are consistent with the idea that parental influences establish stable phenotypic variation in the offspring through effects on intracellular signaling pathways that regulate the epigenetic state and function of specific regions of the genome.
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ISSN:0893-133X
1740-634X
1740-634X
DOI:10.1038/npp.2012.149