Psychology Department, University of Wisconsin-Madison, Madison, WI, USA.
Epigenetics. 2012 Mar;7(3):230-8. doi: 10.4161/epi.7.3.19265.
Several neurodevelopmental disorders are marked by atypical Methyl-CpG-binding protein 2 (MeCP2) expression or function; however, the role of MeCP2 is complex and not entirely clear. Interestingly, there are sex differences in some of these disorders, and it appears that MeCP2 has sex-specific roles during development. Specifically, recent data indicate that a transient reduction in MeCP2 within developing amygdala reduces juvenile social play behavior in males to female-typical levels. These data suggest that MeCP2 within the amygdala is involved in programming lasting sex differences in social behavior. In the present study, we infused MeCP2 or control siRNA into the amygdala of male and female rats during the first three days of postnatal life in order to assess the impact of a transient reduction in MeCP2 on arginine vasopressin (AVP), a neural marker that is expressed differentially between males and females and is linked to a number of social behaviors. The expression of AVP, as well as several other genes, was measured in two-week old and adult animals. Two-week old males expressed more AVP and galanin mRNA in the amygdala than females, and a transient reduction in MeCP2 eliminated this sex difference by reducing the expression of both gene products in males. A transient reduction in MeCP2 also decreased androgen receptor (AR) mRNA in two-week old males. In adulthood, control males had more AVP-immunoreactive (AVP-ir) cells than females in the centromedial amygdala (CMA), bed nucleus of the stria terminalis (BST) and in the fibers that project from these cells to the lateral septum (LS). A transient reduction in MeCP2 eliminated this sex difference. Interestingly, there were no lasting differences in galanin or AR levels in adulthood. Reducing MeCP2 levels during development did not alter estrogen receptorα, neurofilament or Foxg1. We conclude that a transient reduction in MeCP2 expression in the developing male amygdala has a transient impact on galanin and AR expression but a lasting impact on AVP expression, highlighting the importance of MeCP2 in organizing sex differences in the amygdala.
几种神经发育障碍的特点是甲基化-CpG 结合蛋白 2（MeCP2）的表达或功能异常；然而，MeCP2 的作用很复杂，并不完全清楚。有趣的是，这些疾病中的一些存在性别差异，而且似乎在发育过程中 MeCP2 具有性别特异性作用。具体来说，最近的数据表明，在发育中的杏仁核中 MeCP2 的短暂减少会降低雄性的青少年社交玩耍行为，使其达到雌性的典型水平。这些数据表明，杏仁核中的 MeCP2 参与了编程社交行为的持久性别差异。在本研究中，我们在新生后三天内将 MeCP2 或对照 siRNA 注入雄性和雌性大鼠的杏仁核中，以评估 MeCP2 的短暂减少对精氨酸加压素（AVP）的影响，AVP 是一种在雄性和雌性之间表达差异的神经标记物，与许多社交行为有关。在两周大和成年动物中测量了 AVP 以及其他几种基因的表达。两周大的雄性杏仁核中的 AVP 和甘丙肽 mRNA 表达高于雌性，而 MeCP2 的短暂减少通过减少雄性两种基因产物的表达消除了这种性别差异。MeCP2 的短暂减少也降低了两周大雄性的雄激素受体（AR）mRNA。在成年期，对照雄性的中央杏仁核（CMA）、终纹床核（BST）和这些细胞投射到侧隔核（LS）的纤维中的 AVP-免疫反应性（AVP-ir）细胞多于雌性。MeCP2 的短暂减少消除了这种性别差异。有趣的是，成年期甘丙肽或 AR 水平没有持久差异。在发育过程中降低 MeCP2 水平不会改变雌激素受体α、神经丝或 Foxg1。我们得出结论，发育中的雄性杏仁核中 MeCP2 表达的短暂减少对甘丙肽和 AR 表达有短暂影响，但对 AVP 表达有持久影响，突出了 MeCP2 在组织杏仁核中的性别差异方面的重要性。
