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 have been demonstrated in some people with autism and can be modeled in rats by exposure to valproic acid during neural tube closure. Reductions in Purkinje cell number and cerebellar volume, particularly of the posterior lobe, have also been reported in people with autism. Thus, a stereological examination of cerebellar morphology was undertaken in valproate-exposed rats. Compared to controls, rats exposed to a single dose of 600-mg/kg sodium valproate on embryonic day 12.5 had significantly fewer Purkinje cells in the cerebellar vermis and a reduction short of significant in the hemispheres. The diminished cell numbers reflect reductions in tissue volume throughout the cerebellum, rather than cell density, which was unaffected in all regions. Within the vermis, the reduction in volume was significantly greater in the posterior lobe than in the anterior lobe. The results parallel those reported for human cases of autism.
Ingram
J L
JL
Department of Obstetrics and Gynecology, University of Rochester School of Medicine and Dentistry, 14642, Rochester, NY, USA.
Peckham
S M
SM
Tisdale
B
B
Rodier
P M
PM
D000818:Animals; D000927:Anticonvulsants / Q000633:toxicity*; D001321:Autistic Disorder / Q000139:chemically induced* / Q000523:psychology*; D001522:Behavior, Animal / Q000187:drug effects*; D002452:Cell Count; D002526:Cerebellar Diseases / Q000139:chemically induced* / Q000473:pathology / Q000523:psychology*; D005260:Female; D011247:Pregnancy; D011689:Purkinje Cells / Q000187:drug effects / Q000473:pathology; D051381:Rats; D020318:Rats, Long-Evans; D014635:Valproic Acid / Q000633:toxicity*
D000927:Anticonvulsants; D014635:Valproic Acid