Weaver Ian C G, Meaney Michael J, Szyf Moshe
Douglas Hospital Research Center, Montréal, QC, Canada.
Proc Natl Acad Sci U S A. 2006 Feb 28;103(9):3480-5. doi: 10.1073/pnas.0507526103. Epub 2006 Feb 16.
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.
早期生活经历对成年个体的行为和应激反应具有长期影响。我们之前提出，早期生活经历会导致海马体中糖皮质激素受体基因表达的稳定表观遗传编程。本研究的目的是探讨早期生活经历对后代海马体转录组的整体影响以及应激介导行为的发展，以及这些影响在成年期是否可逆。成年后代被中枢注射生理盐水、组蛋白去乙酰化酶抑制剂曲古抑菌素A（TSA）或必需氨基酸L-甲硫氨酸。在一个陌生的旷场 arena 中对动物进行评估，并通过微阵列分析评估每只动物的海马体转录组。在此我们报告，TSA 和甲硫氨酸处理逆转了母性照料对旷场行为的影响。我们鉴定出超过900个受母性照料稳定调控的基因。这些基因表达差异中的一部分可通过组蛋白去乙酰化酶抑制剂 TSA 或甲基供体 L-甲硫氨酸逆转。这些结果表明，早期生活经历对海马体转录组和焦虑介导行为具有稳定而广泛的影响，这在成年期可能是可逆的。
