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

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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.