National Demonstration Center for Experimental Fisheries Science Education, Shanghai Ocean University, Shanghai 201306, China; Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Shanghai Ocean University, Ministry of Education, Shanghai 201306, China.
National Demonstration Center for Experimental Fisheries Science Education, Shanghai Ocean University, Shanghai 201306, China; Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Shanghai Ocean University, Ministry of Education, Shanghai 201306, China; International Research Center for Marine Biosciences at Shanghai Ocean University, Ministry of Science and Technology, Shanghai 201306, China.
Comp Biochem Physiol C Toxicol Pharmacol. 2024 Jan;275:109783. doi: 10.1016/j.cbpc.2023.109783. Epub 2023 Nov 4.
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.
丙戊酸（VPA）是一种有效的药物，常用于治疗癫痫和各种癫痫发作。然而，VPA 有许多与自闭症谱系障碍（ASD）相关的副作用。因此，我们在 VPA 暴露后的成年主动斑马鱼中进行了分子和行为测试，以研究基因转录变化、社交行为、攻击行为、焦虑和运动。我们的研究结果表明，VPA 暴露会产生类似 ASD 的表型和行为：与自闭症相关的基因，如 adsl、mbd5 和 shank3a 发生改变；社交互动缺陷。进一步的行为模式表明，VPA 暴露会显著降低攻击行为，增加焦虑行为和体内皮质醇水平。VPA 暴露不会影响斑马鱼的运动活性。此外，我们还使用相关分析来研究 ASD 相关基因与不同行为测试之间的稳健性，结果表明，ASD 相关基因与攻击行为呈负相关。我们的研究表明，攻击行为测定是 VPA 神经毒性行为的更好预测指标。
