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，怀孕早期接触VPA会增加儿童患自闭症障碍的风险。本研究从VPA的药理作用、对组蛋白脱乙酰酶的抑制作用等方面，探讨了VPA处理后大鼠胎脑组织中组蛋白修饰与脑组织形态变化的关系。在SD、F344和Wistar京都(WK)大鼠胚胎中，在GD11进行VPA治疗后的第16天(GD)，检测到皮质神经元迁移的中断。然而，在SD大鼠胎脑中观察到异常的神经运动束，而在F344和WK大鼠胎脑中未观察到，这表明胎脑的“某些”形态变化部分是由遗传因素引起的。在出生后第11天的新生儿功能观察中，通过分析母体衍生后给予VPA治疗的新生儿的c-Fos免疫反应细胞的分布，发现了异常的脑功能，如恐惧反应增加。由于不同品系大鼠对VPA的敏感性不同，本研究未能如期进行。因此，在本研究期间，VPA修饰组蛋白对大鼠胎脑形态变化的影响尚未被揭示。

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.