Prenatal exposure of rats to valproic acid reproduces the cerebellar anomalies associated with autism

Abnormalities in anatomy and function of the cranial nerve motor nuclei hav e been demonstrated in some people with autism and can be modeled in rats b y exposure to valproic acid during neural tube closure. Reductions in Purki nje cell number and cerebellar volume, particularly or the posterior lobe, have also been reported in people with autism. Thus, a stereological examin ation of cerebellar morphology was undertaken in valproate-exposed rats. Co mpared to controls, rats exposed to a single dose of 600-mg/kg sodium valpr oate on embryonic day 12.5 had significantly fewer Purkinje cells in the ce rebellar vermis and a reduction short of significant in the hemispheres. Th e diminished cell numbers reflect reductions in tissue volume throughout th e cerebellum, rather than cell density, which was unaffected in all regions . Within the vermis. the reduction in volume was significantly greater in t he posterior lobe than in the anterior lobe. The results parallel those rep orted for human cases of autism. (C) 2000 Elsevier Science Inc. All rights reserved.