Document Detail

Variations in postnatal maternal care and the epigenetic regulation of metabotropic glutamate receptor 1 expression and hippocampal function in the rat.
MedLine Citation:
PMID:  23045678     Owner:  NLM     Status:  MEDLINE    
Variations in maternal care in the rat affect hippocampal morphology and function as well as performance on hippocampal-dependent tests of learning and memory in the offspring. Preliminary genome-wide analyses of gene transcription and DNA methylation of the molecular basis for such maternal effects suggested differences in the epigenetic state and transcriptional activity of the Grm1 gene in the rat as a function of maternal care. Grm1 encodes the type I metabotropic glutamate receptor (mGluR1), and we found increased mGluR1 mRNA and protein in hippocampus from the adult offspring of mothers showing an increased frequency of pup licking/grooming (i.e., high-LG mothers) that was associated with a decrease in the methylation of Grm1. ChIP assays showed increased levels of histone 3 lysine 9 acetylation and histone 3 lysine 4 trimethylation of Grm1 in hippocampus from the adult offspring of high-LG compared with low-LG mothers. These histone posttranslational modifications were highly correlated, and both associate inversely with DNA methylation and positively with transcription. Studies of mGluR1 function showed increased hippocampal mGluR1-induced long-term depression in the adult offspring of high-LG compared with low-LG mothers, as well as increased paired-pulse depression (PPD). PPD is an inhibitory feedback mechanism that prevents excessive glutamate release during high-frequency stimulation. The maternal effects on both long-term depression and PPD were eliminated by treatment with an mGluR1-selective antagonist. These findings suggest that variations in maternal care can influence hippocampal function and cognitive performance through the epigenetic regulation of genes implicated in glutamatergic synaptic signaling.
Rosemary C Bagot; Tie-Yuan Zhang; Xianglan Wen; Thi Thu Thao Nguyen; Huy-Binh Nguyen; Josie Diorio; Tak Pan Wong; Michael J Meaney
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-10-08
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  109 Suppl 2     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-17     Completed Date:  2013-01-16     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  17200-7     Citation Subset:  IM    
Neuroscience Division, Douglas Mental Health University Institute, Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada.
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MeSH Terms
Base Sequence
Behavior, Animal / physiology
DNA / genetics
DNA Methylation
Epigenesis, Genetic
Gene Expression Regulation
Genome-Wide Association Study
Hippocampus / physiology*
Histones / metabolism
Long-Term Potentiation
Long-Term Synaptic Depression
Maternal Behavior / physiology*
Molecular Sequence Data
Promoter Regions, Genetic
RNA, Messenger / genetics,  metabolism
Rats, Long-Evans
Receptors, Metabotropic Glutamate / antagonists & inhibitors,  genetics*,  metabolism*
Grant Support
//Canadian Institutes of Health Research
Reg. No./Substance:
0/Histones; 0/RNA, Messenger; 0/Receptors, Metabotropic Glutamate; 0/metabotropic glutamate receptor 5; 0/metabotropic glutamate receptor type 1; 9007-49-2/DNA

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