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Loving mothers ease stress through epigenetics

Nature Reviews Neuroscience volume 5, page 598 (2004)Cite this article

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Stress activates the hypothalamic–pituitary–adrenal (HPA) axis, which increases plasma glucocorticoid levels. By means of a negative-feedback loop, glucocorticoids dampen the HPA response. In adult rats that enjoyed high levels of maternal care in their first week of life, glucocorticoid receptor (GR) expression in the hippocampus is increased, making the whole HPA axis more sensitive to glucocorticoid feedback. Possible mechanisms have been suggested for how maternal care might acutely increase GR expression, but how this effect is maintained throughout life remains a mystery.

The regulation of gene transcription is highly complex, and one mechanism that is involved is DNA methylation. Weaver et al. compared methylation of the GR promoter in the adult offspring of high-caring and low-caring dams. In the 'high-care' group, methylation of a particular cytosine in the binding site for the transcription factor NGFI-A was 90% less than in the 'low-care' group. This cytosine is highly methylated in newborn pups of either high- or low-caring dams, but in pups that were nursed (not necessarily born) by a high-caring dam, methylation dropped within six days, and remained low thereafter. Reduced methylation correlated with increased NGFI-A binding to the promoter, which is expected to increase GR transcription.

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References

ORIGINAL RESEARCH PAPER

  1. Weaver, I. C. G. et al. Epigenetic programming by maternal behavior. Nature Neuroscience 27 June 2004 (doi:10.1038/nn1276)

FURTHER READING

  1. Meaney, M. J. Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations. Annu. Rev. Neurosci. 24, 1161–1192 (2001)

    Article  CAS  Google Scholar 

  2. Gross, C. & Hen, R. The developmental origins of anxiety. Nature Rev. Neurosci. 5, 545–552 (2004)

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Associate Editor, Nature Neuroscience,

    Annette Markus

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  1. Annette Markus
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Markus, A. Loving mothers ease stress through epigenetics. Nat Rev Neurosci 5, 598 (2004). https://doi.org/10.1038/nrn1483

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