Wright E C, Johnson S A, Hao R, Kowalczyk A S, Greenberg G D, Ordoñes Sanchez E, Laman-Maharg A, Trainor B C, Rosenfeld C S
Department of Psychology, University of California, Davis, CA, USA.
Bond Life Science Center, University of Missouri, Columbia, MO, USA.
J Neuroendocrinol. 2017 Jun;29(6). doi: 10.1111/jne.12475.
Chemical and psychological stressors can exert long lasting changes in brain function and behaviour. Changes in DNA methylation have been shown to be an important mechanism mediating long lasting changes in neural function and behaviour, especially for anxiety-like or stress responses. In the present study, we examined the effects of either a social or chemical stressor on DNA methyltransferase (DNMT) gene expression in the amygdala, an important brain region modulating stress responses and anxiety. In adult California mice (Peromyscus californicus) that were naïve to social defeat, females had higher levels of Dnmt1 expression in punch samples of the central amygdala (CeA) than males. In addition, mice that underwent social defeat stress showed reduced Dnmt1 and Dnmt3a expression in the CeA of females but not males. A second study using more anatomically specific punch samples replicated these effects for Dnmt1. Perinatal exposure (spanning from periconception through lactation) to bisphenol A or ethinyl oestradiol (oestrogens in birth control pills) also abolished sex differences in Dnmt1 expression in the CeA but not the basolateral amygdala. These findings identify a robust sex difference in Dnmt1 expression in the CeA that is sensitive to both psychological and chemical stressors. Future studies should aim to examine the impact of psychological and chemical stressors on DNA methylation in the CeA and also investigate whether Dnmt1 may have an underappreciated role in plasticity in behaviour.
化学和心理应激源可对大脑功能和行为产生持久的改变。DNA甲基化的变化已被证明是介导神经功能和行为持久变化的重要机制，尤其是对于焦虑样或应激反应。在本研究中，我们研究了社会应激源或化学应激源对杏仁核中DNA甲基转移酶（DNMT）基因表达的影响，杏仁核是调节应激反应和焦虑的重要脑区。在未经历过社会挫败的成年加利福尼亚小鼠（加州林鼠）中，雌性小鼠中央杏仁核（CeA）打孔样本中的Dnmt1表达水平高于雄性。此外，经历过社会挫败应激的小鼠，雌性CeA中的Dnmt1和Dnmt3a表达降低，而雄性则未出现这种情况。另一项使用解剖学上更具特异性的打孔样本的研究重复了Dnmt1的这些效应。围产期暴露（从受孕前到哺乳期）于双酚A或乙炔雌二醇（避孕药中的雌激素）也消除了CeA中Dnmt1表达的性别差异，但基底外侧杏仁核中未消除。这些发现确定了CeA中Dnmt1表达存在明显的性别差异，且该差异对心理和化学应激源均敏感。未来的研究应旨在研究心理和化学应激源对CeA中DNA甲基化的影响，并调查Dnmt1在行为可塑性中是否可能具有未被充分认识的作用。
