Maternal care effects on the hippocampal transcriptome and anxiety-mediated behaviors in the offspring that are reversible in adulthood

  • Ian C. G. Weaver
    *Douglas Hospital Research Center, 6875 LaSalle Boulevard, Montréal, QC, Canada H4H 1R3; and
  • Michael J. Meaney
    *Douglas Hospital Research Center, 6875 LaSalle Boulevard, Montréal, QC, Canada H4H 1R3; and
  • Moshe Szyf
    McGill Program for the Study of Behaviour, Genes, and Environment and

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<jats:p> 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 <jats:sc>l</jats:sc> -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 <jats:sc>l</jats:sc> -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. </jats:p>

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