4.2 Article

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

Journal

IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES
Volume 26, Issue 3, Pages 316-325

Publisher

MASHHAD UNIV MED SCIENCES
DOI: 10.22038/IJBMS.2023.68165.14889

Keywords

Autism spectrum disorder; Oxytocin receptor; Shank3; Social behavior; Zebrafish

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Autism is a complex neurodevelopmental disorder characterized by social interaction deficiencies, hyperactivity, anxiety, communication disorders, and a limited range of interests. Zebrafish is a social vertebrate used as a biomedical research model to understand social behavior mechanisms.
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 mu M) 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 mu M 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 mu M 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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