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Reversal of maternal programming of stress responses in adult offspring through methyl supplementation: altering epigenetic marking later in life.
- Source :
-
The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2005 Nov 23; Vol. 25 (47), pp. 11045-54. - Publication Year :
- 2005
-
Abstract
- Stress responses in the adult rat are programmed early in life by maternal care and associated with epigenomic marking of the hippocampal exon 1(7) glucocorticoid receptor (GR) promoter. To examine whether such epigenetic programming is reversible in adult life, we centrally infused the adult offspring with the essential amino acid L-methionine, a precursor to S-adenosyl-methionine that serves as the donor of methyl groups for DNA methylation. Here we report that methionine infusion reverses the effect of maternal behavior on DNA methylation, nerve growth factor-inducible protein-A binding to the exon 1(7) promoter, GR expression, and hypothalamic-pituitary-adrenal and behavioral responses to stress, suggesting a causal relationship among epigenomic state, GR expression, and stress responses in the adult offspring. These results demonstrate that, despite the inherent stability of the epigenomic marks established early in life through behavioral programming, they are potentially reversible in the adult brain.
- Subjects :
- Aging
Animals
Animals, Newborn
Behavior, Animal
Early Growth Response Protein 1 metabolism
Female
Hypothalamo-Hypophyseal System physiopathology
Methionine pharmacology
Pituitary-Adrenal System physiopathology
Promoter Regions, Genetic
Rats
Rats, Long-Evans
Receptors, Glucocorticoid metabolism
Stress, Physiological psychology
DNA Methylation drug effects
Epigenesis, Genetic
Hippocampus metabolism
Maternal Behavior
Receptors, Glucocorticoid genetics
Stress, Physiological physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2401
- Volume :
- 25
- Issue :
- 47
- Database :
- MEDLINE
- Journal :
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 16306417
- Full Text :
- https://doi.org/10.1523/JNEUROSCI.3652-05.2005