The effects of valproic acid neurotoxicity on aggressive behavior in zebrafish autism model

Abstract

Valproic acid (VPA) is an effective drug, which is preferred for the treatments of epilepsy and various kinds of seizures. Nonetheless, VPA has many side effects associated with autism spectrum disorder (ASD). Therefore, we conducted molecular and behavior tests in adult proactive zebrafish after VPA exposure to investigate gene transcription changes, social behavior, aggression, anxiety and locomotion. Our findings revealed that VPA exposure generates ASD-like phenotypes and behaviors: genes associated with autism, such as adsl, mbd5 and shank3a altered; social interaction deficit. Further behavioral patterns suggest that VPA exposure induces decreases in aggression and increases the anxiety behavior and body cortisol significantly. VPA exposure did not affect locomotor activity in zebrafish. Additionally, we used correlative analyses to investigate the robustness between the ASD-related genes and the different behavior tests, results showed that ASD-related genes are negatively associated with aggressive behavior. Our study demonstrated that aggressive behavior assay is a better predictor of behavior for neurotoxicology of VPA.