Nanosilibinin ameliorates anxiety, learning impairment and Wnt-β catenin related genes expression deficits in zebrafish model of Autism Spectrum Disorder

purpose The present study evaluated the effect of Nanosilibinin (as an inhibitor of Wnt signaling pathway), on neurobehavioral and molecular deficits in Valproic acid zebrafish model of Autism Spectrum Disorder. Methods: Zebrafish embryos were exposed to Valproic acid (1µM) and Nanosilibinin (100,200 and 500 µM) for 96 h, then survival rate, inattentive and anxiety behavior and the expression of CHD8, CTNNB, GSK3β, LRP6, TNFα, IL1β and BDNF genes were assessed 7 days post fertilization (dpf). Results: The results indicated that except 500 µM, other concentrations of Nanosilibinin didn’t have any adverse effect on survival, hatching and morphological development when were used with Valproic acid at the same time. In addition, 100 and 200 µM of Nanosilibinin could ameliorate the anxiety and learning deficit in zebrafish larvae. Real-time analysis revealed that Nanosilibinin prevented raising the expression of a number of genes associated with autism such as CHD8, CTNNB, GSK3 β, LRP6, TNFα, IL1β and BDNF after exposure to Valproic acid. Conclusion: In conclusion, Nanosilibinin treatment for the first 96 h of life showed therapeutic effect on an ASD-like phenotype by decreasing anxiety and learning deficits and reduction in expression of number ASD related genes.