Department of Psychological and Brain Sciences, University of Delaware, Newark, Delaware, USA.
Dev Psychobiol. 2022 Mar;64(3):e22231. doi: 10.1002/dev.22231.
Exposure to adversity in early development has powerful and potentially lasting consequences on behavior. Previous work in our laboratory using female Long-Evans rats has demonstrated that exposure to early-life maltreatment manifests into alterations in dam behavior, including a perpetuation of the maltreatment phenotype. These observed behavioral changes coincide with changes in epigenetic activity in the prefrontal cortex (PFC). Further, treating dams with a chromatin modifying agent (Zebularine) normalizes methylation and maltreatment phenotypes, suggesting a link between epigenetic programming and phenotypic outcomes. Here, we sought to investigate if administration of a chromatin modifying agent concurrent with the experience of maltreatment normalizes epigenetic activity associated with maltreatment and alters behavioral trajectories. Administration of valproic acid (VPA) transiently lowered levels of global DNA methylation in the PFC, regardless of exposure to nurturing care or maltreatment. When VPA-exposed animals reached adulthood, they engaged in more adverse behaviors toward their offspring. These data provide further evidence linking epigenetic changes in the developing brain with effects on behavior.
早期发展中的逆境暴露对行为有强大且潜在持久的影响。我们实验室之前使用雌性长耳大仓鼠的研究表明，早期生活虐待会表现为母性行为的改变，包括虐待表型的持续存在。这些观察到的行为变化与前额叶皮层 (PFC) 中的表观遗传活性变化一致。此外，用染色质修饰剂（泽布替尼）治疗母鼠可使甲基化和虐待表型正常化，这表明表观遗传编程和表型结果之间存在联系。在这里，我们试图研究在经历虐待的同时给予染色质修饰剂是否能使与虐待相关的表观遗传活性正常化，并改变行为轨迹。丙戊酸 (VPA) 的给药会短暂降低 PFC 中的全基因组 DNA 甲基化水平，而无论是否接触过养育关怀或虐待。当 VPA 暴露的动物成年后，它们会对自己的后代表现出更多的不良行为。这些数据进一步证明了发育中的大脑中的表观遗传变化与行为的影响之间存在联系。
