Efeito do extrato de Hypericum Perforatum em modelo animal de autismo induzido por exposição pré-natal ao ácido valpróico

Abstract

Introduction: Autism Spectrum Disorders (ASD) are characterized by the presence of restricted interest, repetitive movements and social and communication deficits. Males are more affected for this condition and present high prevalence. Exposure to valproic acid (VPA) during the embryonic period increases the incidence of the disorder, a fact that has been used to obtain an animal model of autism. Patients and mice that replicate characteristics of ASD showed behavioral deficits and repetitive movements, as well as a reduction in the expression of the Transient Receptor Potential Cation Channel Subfamily C Member 6 (TRPC6) cation channel and in the Gamma-Amino Butyric Acid (GABA) levels. Hypericum perforatum (HP) can act on these pathways by rescuing behavioral changes and TRPC6 levels and blocking GABA uptake. Objective: To evaluate the effect of HP in juvenile rats prenatally exposed to VPA, through behavioral tests (open field, new object recognition, social interaction and elevated plus maze) and neuronal quantification of the hippocampus. Material and Methods: Pregnant rats were treated on embryonic day 12.5 with an intraperitoneal injection of 600 mg/kg of VPA or 1 ml/100g of saline solution (SS). From the 24th to the 30th postnatal day, the male pups were treated, every 12 hours, with 1 ml/100g of SS or with 1g/Kg of HP, by gavage (total of 14 doses). In the following days, the animals’ behavior was evaluated in the open field, recognition of the new object, social interaction and elevated plus maze tests (one test per day). Finally, the animals' brains were processed in paraffin, stained with hematoxylin and eosin and analyzed for neuronal density in the bilateral dorsal hippocampus. Results: Rats from the SS-SS and SS-HP groups (exposed to SS during the prenatal period) showed normal body morphology while 78% of the groups exposed to prenatal VPA (VPA-SS and VPA-HP) presented deformity in the tail (shorter and with a callus). Eye opening occurred between DPN14 and 16 in all groups, and no statistically significant differences were identified, between the four groups of pups, in the weight curve or in the behavior expressed in the open field tests, new object recognition, social interaction and the elevated plus maze. Conclusions: Young male rats exposed prenatally to VPA showed morphological alterations without ASD-like behavioral features. Such a condition can be justified by an absence of genetic susceptibility of animals exposed to VPA. Due to the lack of reproduction of ASD-like features, it was not possible to evaluate the effect of Hypericum perforatum, which was devoid of adverse effects and seems to be beneficial for memory acquisition.