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 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.
Weaver
Ian C G
IC
Douglas Hospital Research Center, Montréal, QC, Canada.
Meaney
Michael J
MJ
Szyf
Moshe
M
D000375:Aging / Q000235:genetics / Q000502:physiology* / Q000523:psychology; D000818:Animals; D001007:Anxiety / Q000235:genetics* / Q000523:psychology; D001522:Behavior, Animal / Q000502:physiology*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006877:Hydroxamic Acids / Q000494:pharmacology; D008425:Maternal Behavior / Q000502:physiology*; D008715:Methionine / Q000494:pharmacology; D009035:Mothers; D009419:Nerve Tissue Proteins / Q000235:genetics; D011506:Proteins / Q000235:genetics; D051381:Rats; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics*; D062085:RNA, Long Noncoding
D015816:Cell Adhesion Molecules, Neuronal; D004265:DNA Helicases; D016326:Extracellular Matrix Proteins; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases; D006877:Hydroxamic Acids; D008715:Methionine; D009419:Nerve Tissue Proteins; D011506:Proteins; D000091042:Reelin Protein; D012697:Serine Endopeptidases; C497681:vof-16 long non-coding RNA, rat; D062085:RNA, Long Noncoding; C012589:trichostatin A