title: Maternal licking regulates hippocampal glucocorticoid receptor transcription through a thyroid hormone-serotonin-NGFI-A signalling cascade.
abstract: 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 1(7)) 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 1(7) 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 1(7) 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.
authors: Sackler Program for Epigenetics and Psychobiology,  Douglas Mental Health University Institute, McGill University, , 6875 Boul. LaSalle, Montréal, Québec,  Canada , H4H1R3.
authors: Ian C
authors: IC
authors: Hellstrom
authors: Sabine K
authors: SK
authors: Dhir
authors: Josie C
authors: JC
authors: Diorio
authors: Michael J
authors: MJ
authors: Meaney
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D051766:Early Growth Response Protein 1 / Q000378:metabolism; D005091:Exons; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D016086:Lentivirus / Q000235:genetics / Q000378:metabolism; D008297:Male; D008425:Maternal Behavior; D061251:Primary Cell Culture; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D051381:Rats; D020318:Rats, Long-Evans; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D012701:Serotonin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013974:Thyroxine / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014284:Triiodothyronine / Q000235:genetics / Q000378:metabolism
chemical_list: D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D011965:Receptors, Glucocorticoid; D014284:Triiodothyronine; D012701:Serotonin; D013974:Thyroxine