Philosophical Transactions of the Royal Society B: Biological Sciences
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Maternal licking regulates hippocampal glucocorticoid receptor transcription through a thyroid hormone–serotonin–NGFI-A signalling cascade

Ian C. Hellstrom

Ian C. Hellstrom

Sackler Program for Epigenetics and Psychobiology, Douglas Mental Health University Institute, McGill University, 6875 Boul. LaSalle, Montréal, Québec, Canada H4H1R3

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Sabine K. Dhir

Sabine K. Dhir

Sackler Program for Epigenetics and Psychobiology, Douglas Mental Health University Institute, McGill University, 6875 Boul. LaSalle, Montréal, Québec, Canada H4H1R3

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Josie C. Diorio

Josie C. Diorio

Sackler Program for Epigenetics and Psychobiology, Douglas Mental Health University Institute, McGill University, 6875 Boul. LaSalle, Montréal, Québec, Canada H4H1R3

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Michael J. Meaney

Michael J. Meaney

Sackler Program for Epigenetics and Psychobiology, Douglas Mental Health University Institute, McGill University, 6875 Boul. LaSalle, Montréal, Québec, Canada H4H1R3

Singapore Institute for Clinical Science, 30 Medical Drive, Singapore 117609

[email protected]

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Published:https://doi.org/10.1098/rstb.2012.0223

    Variations in parental care direct phenotypic development across many species. Variations in maternal pup licking/grooming (LG) in the rat regulate the development of individual differences in hypothalamic–pituitary–adrenal responses to stress. The adult offspring of mothers that show an increased frequency of pup LG have increased hippocampal glucocorticoid receptor (GR) expression and more modest pituitary–adrenal responses to stress. This parental effect is mediated by the epigenetic programming of a GR exon 1 promoter (exon 17) through the binding of the transcription factor nerve growth factor-inducible factor A (NGFI-A). In this paper, we report that: (i) the association of NGFI-A with the exon 17 GR promoter is dynamically regulated by mother–pup interactions; (ii) this effect is mimicked by artificial tactile stimulation comparable to that provided by pup LG; (iii) that serotonin (5-HT) induces an NGFI-A-dependent increase in GR transcription in hippocampal neurons and NGFI-A overexpression is sufficient for this effect; and (iv) that thyroid hormones and 5-HT are key mediators of the effects of pup LG and tactile stimulation on NGFI-A binding to the exon 17 GR promoter in hippocampus. These findings suggest that pup LG directly activates 5-HT systems to initiate intracellular signalling pathways in the hippocampus that regulate GR transcription.

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