Multiple environmental agents, including medical drugs, have been associated with an increased risk of autism. In autism, some structural abnormalities in the cerebellum have been reported. Especially, a reduction in size and number of Purkinje cells is revealed in both the postmortem human studies and Valproate (VPA)-administrated adult animals.
Now we investigated the effects of prenatal administration of drugs known as inducers of autism, and observed their postnatal cerebellar development in rat. VPA is an antiepileptic drug positively correlated with the occurrence of autism. VPA was once administrated to embryonic day 16 p.o., and the cerebellum in pups was observed from young age to matured age. In addition, chlorpyrifos (CPF), which is popular pesticide and known as autistic inducer, was also administrated to same day and compared its effect to VPA. In normal cerebellar development, the soma of Purkinje cells form a single cell layer from multi cell layer, and elongate their dendrites with synapses during the first two weeks. In VPA administrated rat, the elongation of Purkinje cell dendrites started earlier and reached all over the molecular layer even in P12, while they formed even multi cell layer. In young cerebellum of VPA-administrated rat, the lobules in the vermis developed earlier and formed excess gyrus in the anterior lobe, specifically in lobules V, VI and VII, although these exsess gyrus was disappeared in mature cerebellum. In human, transient abnormal growth trend of the autistic cerebellum was reported. It was suggested that VPA-induced epigenetic effects would change the developmental progress in immature cerebellum and corrupt the cerebellar networks through adulthood.

研究助成：Research funds : KAKENHI26350498