Oxytocin protective effects on zebrafish larvae models of autism-like spectrum disorder

Objective(s): Autism is a complicated neurodevelopmental disorder characterized by social interaction deficiencies, hyperactivity, anxiety, communication disorders, and a limited range of interests. The zebrafish (Danio rerio) is a social vertebrate used as a biomedical research model to understand social behavior mechanisms. Materials and Methods: After spawning, the eggs were exposed to sodium valproate for ۴۸ hr, after which the eggs were divided into eight groups. Except for the positive and control groups, there were six treatment groups based on oxytocin concentration (۲۵, ۵۰, and ۱۰۰ μM) and time point (۲۴ and ۴۸ hr). Treatment was performed on days ۶ and ۷, examined by labeling oxytocin with fluorescein-۵-isothiocyanate (FITC) and imaging with confocal microscopy and the expression levels of potential genes associated with the qPCR technique. Behavioral studies, including light-dark background preference test, shoaling behavior, mirror test, and social preference, were performed on ۱۰, ۱۱, ۱۲, and ۱۳ days post fertilization (dpf), respectively.Results: The results showed that the most significant effect of oxytocin was at the concentration of ۵۰ μM and the time point of ۴۸ hr. Increased expression of shank۳a, shank۳b, and oxytocin receptor genes was also significant at this oxytocin concentration. Light-dark background preference results showed that oxytocin in the concentration of ۵۰ µM significantly increased the number of crosses between dark and light areas compared with valproic acid (positive group). Also, oxytocin showed an increase in the frequency and time of contact between the two larvae. We showed a decrease in the distance in the larval group and an increase in time spent at a distance of one centimeter from the mirror. Conclusion: Our findings showed that the increased gene expression of shank۳a, shank۳b, and oxytocin receptors improved autistic behavior. Based on this study some indications showed that oxytocin administration in the larval stage could significantly improve the autism-like spectrum.

کلیدواژه ها:

Autism spectrum disorder ، Oxytocin receptor ، Social behavior ، Zebrafish