Histone modification in a rat fetal brain an neuronal network formation in a rat neonate after prenatal valproic acid treatment.

临床报告显示，怀孕早期暴露于VPA会增加儿童患自闭症的风险。在这项研究中，集中在VPA药理作用，抑制组蛋白脱乙酰酶，组蛋白修饰和VPA处理后大鼠胎脑形态学变化之间的关系进行了检查。在妊娠第11天VPA给药后第16天（GD），在SD、F344和Wistar京都（WK）大鼠胎仔中检测到皮质神经元迁移中断。然而，在SD大鼠胎脑中观察到异常的神经走行束，而在F344或WK大鼠胎脑中未观察到异常的神经走行束，表明胎脑中的“某些”形态学改变部分是由于遗传因素。在出生后第11天对新生儿进行的功能观察中，通过分析产前接受VPA治疗的新生儿母体衍生后c-Fos免疫反应性细胞的分布，发现了异常脑功能，如恐惧反应增加。由于不同品系大鼠对VPA的敏感性不同，研究无法如期进行。因此，VPA修饰组蛋白对大鼠胎脑形态学变化的影响在本研究期间尚未发现。

Clinical reports revealed that VPA exposure during early pregnancy increases the risk of a child having an autistic disorder. In this study, focusing on VPA pharmacological action, inhibition of histone deacetylase, the relationship between histone modification and morphological changes in the rat fetal brain after VPA treatment was examined. Disruption of neuronal migration in the cortex was detected in SD, F344 as well as Wistar Kyoto(WK) rat fetus at the gestational day(GD) 16 after VPA treatment at GD11. However, abnormal neural running tract in the midbrain was observed in SD rat fetal brain, but not in F344 or WK rat fetal brain, indicating that "some" morphological changes in the fetal brain are partly due to genetic factors. In the functional observation of neonates on postnatal day 11, an abnormal brain function, such as an increase in fear response, was identified on analyzing the distribution of c-Fos immunoreactive cells after maternal derivation in neonate treated prenatally with VPA. The study could not go to schedule in order to different sensitivity for VPA among rat strains. Therefore, effects of histone modification by VPA on morphological changes in a rat fetal brain have not revealed in this study period.