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

Document Type : Original Article


1 Department of Aquatic Animal Health, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran

2 Centre of Excellence for Warm Water Fish Health and Disease, Shahid Chamran University of Ahvaz, Ahvaz, Iran

3 Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences (TUMS), Tehran, Iran

4 Department of Toxicology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

5 Oncopathology Research Center, Iran University of Medical Sciences (IUMS), Tehran, Iran

6 Toxicology and Diseases Group (TDG), Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences (TUMS), Tehran, Iran


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 48 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 (25, 50, and 100 μM) and time point (24 and 48 hr). Treatment was performed on days 6 and 7, examined by labeling oxytocin with fluorescein-5-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 10, 11, 12, and 13 days post fertilization (dpf), respectively.
Results: The results showed that the most significant effect of oxytocin was at the concentration of 50 μM and the time point of 48 hr. Increased expression of shank3a, shank3b, and oxytocin receptor genes was also significant at this oxytocin concentration. Light-dark background preference results showed that oxytocin in the concentration of 50 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 shank3a, shank3b, 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.


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