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Featured ArticleDevelopment/Plasticity/Repair

Reversal of Maternal Programming of Stress Responses in Adult Offspring through Methyl Supplementation: Altering Epigenetic Marking Later in Life

Ian C. G. Weaver, Frances A. Champagne, Shelley E. Brown, Sergiy Dymov, Shakti Sharma, Michael J. Meaney and Moshe Szyf
Journal of Neuroscience 23 November 2005, 25 (47) 11045-11054; DOI: https://doi.org/10.1523/JNEUROSCI.3652-05.2005
Ian C. G. Weaver
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Frances A. Champagne
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Shelley E. Brown
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Sergiy Dymov
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Shakti Sharma
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Michael J. Meaney
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Moshe Szyf
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Abstract

Stress responses in the adult rat are programmed early in life by maternal care and associated with epigenomic marking of the hippocampal exon 17 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 17 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.

  • maternal behavior
  • rat
  • hippocampus
  • glucocorticoid receptor
  • epigenetics
  • l-methionine
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The Journal of Neuroscience: 25 (47)
Journal of Neuroscience
Vol. 25, Issue 47
23 Nov 2005
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Reversal of Maternal Programming of Stress Responses in Adult Offspring through Methyl Supplementation: Altering Epigenetic Marking Later in Life
Ian C. G. Weaver, Frances A. Champagne, Shelley E. Brown, Sergiy Dymov, Shakti Sharma, Michael J. Meaney, Moshe Szyf
Journal of Neuroscience 23 November 2005, 25 (47) 11045-11054; DOI: 10.1523/JNEUROSCI.3652-05.2005

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Reversal of Maternal Programming of Stress Responses in Adult Offspring through Methyl Supplementation: Altering Epigenetic Marking Later in Life
Ian C. G. Weaver, Frances A. Champagne, Shelley E. Brown, Sergiy Dymov, Shakti Sharma, Michael J. Meaney, Moshe Szyf
Journal of Neuroscience 23 November 2005, 25 (47) 11045-11054; DOI: 10.1523/JNEUROSCI.3652-05.2005
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