Keller Samantha M, Doherty Tiffany S, Roth Tania L
Department of Psychological and Brain Sciences, University of Delaware, Newark, DE, United States.
Front Behav Neurosci. 2018 Jun 29;12:126. doi: 10.3389/fnbeh.2018.00126. eCollection 2018.
Exposure to adversity early in development alters brain and behavioral trajectories. Data continue to accumulate that epigenetic mechanisms are a mediating factor between early-life adversity and adult behavioral phenotypes. Previous work from our laboratory has shown that female Long-Evans rats exposed to maltreatment during infancy display both aberrant forced swim behavior and patterns of brain DNA methylation in adulthood. Therefore, we examined the possibility of rescuing the aberrant forced swim behavior in maltreated-adult females by administering an epigenome-modifying drug (zebularine) at a dose previously shown to normalize DNA methylation. We found that zebularine normalized behavior in the forced swim test in maltreated females such that they performed at the levels of controls (females that had been exposed to only nurturing care during infancy). These data help link DNA methylation to an adult phenotype in our maltreatment model, and more broadly provide additional evidence that non-targeted epigenetic manipulations can change behavior associated with early-life adversity.
在发育早期接触逆境会改变大脑和行为轨迹。越来越多的数据表明，表观遗传机制是早期生活逆境与成年行为表型之间的一个中介因素。我们实验室之前的研究表明，在婴儿期遭受虐待的雌性Long-Evans大鼠在成年后会表现出异常的强迫游泳行为和大脑DNA甲基化模式。因此，我们研究了通过给予一种表观基因组修饰药物（zebularine，泽布替尼）来挽救受虐待成年雌性大鼠异常强迫游泳行为的可能性，该药物的剂量先前已被证明可使DNA甲基化正常化。我们发现，zebularine使受虐待雌性大鼠在强迫游泳试验中的行为正常化，使其表现达到对照组（在婴儿期仅接受悉心照料的雌性大鼠）的水平。这些数据有助于在我们的虐待模型中将DNA甲基化与成年表型联系起来，更广泛地说，提供了额外的证据，即非靶向表观遗传操作可以改变与早期生活逆境相关的行为。
