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Title:
Maternal care effects on the hippocampal transcriptome and anxiety-mediated behaviors in the offspring that are reversible in adulthood
Authors:
Weaver, Ian C. G.; Meaney, Michael J.; Szyf, Moshe
Affiliation:
AA(Douglas Hospital Research Center, 6875 LaSalle Boulevard, Montréal, QC, Canada H4H 1R3; †McGill Program for the Study of Behaviour, Genes, and Environment; Department of Pharmacology and Therapeutics, McGill University, 3655 Sir William Oslar Promenade, Montréal, QC, Canada H3G 1Y6), AB(Douglas Hospital Research Center, 6875 LaSalle Boulevard, Montréal, QC, Canada H4H 1R3; †McGill Program for the Study of Behaviour, Genes, and Environment; Department of Pharmacology and Therapeutics, McGill University, 3655 Sir William Oslar Promenade, Montréal, QC, Canada H3G 1Y6), AC(Douglas Hospital Research Center, 6875 LaSalle Boulevard, Montréal, QC, Canada H4H 1R3; †McGill Program for the Study of Behaviour, Genes, and Environment; Department of Pharmacology and Therapeutics, McGill University, 3655 Sir William Oslar Promenade, Montréal, QC, Canada H3G 1Y6)
Publication:
Proceedings of the National Academy of Sciences of the United States of America, Volume 103, Issue 9, 2006, pp.3480-3485
Publication Date:
02/2006
Category:
BIOLOGICAL SCIENCES / PSYCHOLOGY
Origin:
PNAS
DOI:
10.1073/pnas.0507526103
Bibliographic Code:
2006PNAS..103.3480W

Abstract

Early-life experience has long-term consequences on behavior and stress responsivity of the adult. We previously proposed that early-life experience results in stable epigenetic programming of glucocorticoid receptor gene expression in the hippocampus. The aim of this study was to examine the global effect of early-life experience on the hippocampal transcriptome and the development of stress-mediated behaviors in the offspring and whether such effects were reversible in adulthood. Adult offspring were centrally infused with saline vehicle, the histone deacetylase inhibitor trichostatin A (TSA), or the essential amino acid l-methionine. The animals were assessed in an unfamiliar open-field arena, and the hippocampal transcriptome of each animal was evaluated by microarray analysis. Here we report that TSA and methionine treatment reversed the effect of maternal care on open-field behavior. We identified >900 genes stably regulated by maternal care. A fraction of these differences in gene expression is reversible by either the histone deacetylase inhibitor TSA or the methyl donor l-methionine. These results suggest that early-life experience has a stable and broad effect on the hippocampal transcriptome and anxiety-mediated behavior, which is potentially reversible in adulthood.
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