Maternal Care Effects on the Hippocampal Transcriptome and Anxiety-Mediated Behaviors in the Offspring That Are Reversible in Adulthood

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...

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Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS 2006-02, Vol.103 (9), p.3480-3485
Hauptverfasser: Weaver, Ian C. G., Meaney, Michael J., Szyf, Moshe
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Sprache:eng
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Zusammenfassung: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0507526103