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

被引:563
作者
Weaver, ICG
Meaney, MJ
Szyf, M
机构
[1] Douglas Hosp, Res Ctr, Dept Psychiat, Verdun, PQ H4H 1R3, Canada
[2] McGill Univ, McGill Program Study Behav Genes & Environm, Montreal, PQ H3G 1Y6, Canada
[3] McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ H3G 1Y6, Canada
关键词
hypothalamic-pituitary-adrenal stress response; L-methionine; maternal behavior; microarray; trichostatin A;
D O I
10.1073/pnas.0507526103
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:3480 / 3485
页数:6
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