Department of Psychological and Brain Sciences, University of Delaware, Newark, DE, 19716, USA.
Sci Rep. 2019 Jul 16;9(1):10253. doi: 10.1038/s41598-019-46539-4.
The quality of parental care received during development profoundly influences an individual's phenotype, including that of maternal behavior. We previously found that female rats with a history of maltreatment during infancy mistreat their own offspring. One proposed mechanism through which early-life experiences influence behavior is via epigenetic modifications. Indeed, our lab has identified a number of brain epigenetic alterations in female rats with a history of maltreatment. Here we sought to investigate the role of DNA methylation in aberrant maternal behavior. We administered zebularine, a drug known to alter DNA methylation, to dams exposed during infancy to the scarcity-adversity model of low nesting resources, and then characterized the quality of their care towards their offspring. First, we replicate that dams with a history of maltreatment mistreat their own offspring. Second, we show that maltreated-dams treated with zebularine exhibit lower levels of adverse care toward their offspring. Third, we show that administration of zebularine in control dams (history of nurturing care) enhances levels of adverse care. Lastly, we show altered methylation and gene expression in maltreated dams normalized by zebularine. These findings lend support to the hypothesis that epigenetic alterations resulting from maltreatment causally relate to behavioral outcomes.
在发育过程中接受的父母照顾的质量深刻地影响个体的表型，包括母性行为。我们之前发现，在婴儿期受到虐待的雌性大鼠会虐待自己的后代。一种被提议的通过早期生活经历影响行为的机制是通过表观遗传修饰。事实上，我们的实验室已经在有虐待史的雌性大鼠中发现了许多大脑表观遗传改变。在这里，我们试图研究 DNA 甲基化在异常母性行为中的作用。我们给在婴儿期暴露于低筑巢资源匮乏逆境模型下的母体施用 zebularine，一种已知能改变 DNA 甲基化的药物，然后描述它们对后代的照顾质量。首先，我们复制了有虐待史的母体虐待自己的后代这一现象。其次，我们表明，用 zebularine 处理的受虐待的母体对其后代表现出较低水平的不良照顾。第三，我们表明，在有养育史的对照母体中给予 zebularine 会增加不良照顾的水平。最后，我们表明 zebularine 使受虐待的母体中的甲基化和基因表达发生改变得到了纠正。这些发现支持了这样一种假设，即虐待引起的表观遗传改变与行为结果有因果关系。
