Congenital malformations in rats prenatally exposed to valproic acid and their relationship with Purkinje cells counts

Introduction: Valproic acid (VPA) is a commonly used drug for the treatment of epilepsy, acute manias and bipolar disorder. It is known that the use of AVP during pregnancy an produce congenital malformations, the fetal valproate syndrome and augment the risk for autism. This disorders haven been modeled in the laboratory by injecting VPA during the embryonic period rats, inducing additionally modifications in the cerebellar anatomy similar to those detected in people with autism. Objective: The goal of this study was to describe some congenital malformations observed in rats exposed prenatally to VPA and its correlation with the number of Purkinje cells from the cerebellar vermis. Methods: VPA (600mg/kg) was applied to pregnant rats during the 12th embrionic day; control rats were injected with saline during the same day. Rats with malformations and control rats were euthanized during the postnatal day 40 and the number of Purkinje cells was determined in sagittal sections from the medial vermis stained with Nissl technique. Results: The prenatal exposure to AVP produced different severity of tail malformations and toe polydactyly, as well as a decrease in the number of Purkinje cells in the lobules VI, VII, VIII y X. A lineal positive correlation between the malformation severity and the number of Purkinje cells was observed in the lobule VIII-B; however, no correlation was detected between those parameters in any additional lobe. Conclusion: There is not correlation between the severity of the malformations produced by VPA and the decrease in the number of Purkinje cells. These findings are relevant for a better understanding of the VPA experimental model in the rat.