Effect of Early Swimming on the Behavior and Striatal Transcriptome of the Shank3 Knockout Rat Model of Autism

Yunchen Meng,1 Dan Xu,1 Weinan Zhang,1 Wenshu Meng,2 Xingyu Lan,3 Xiaoxi Wang,3 Mingjuan Li,3 Xiaoyan Zhang,1 Yu Zhao,1 Haodong Yang,1 Rong Zhang,3– 6 Zhiping Zhen1 1College of P.E and Sports, Beijing Normal University, Beijing, People’s Republic of China; 2College of Life Sciences, Beijing Normal University, Beijing, People’s Republic of China; 3Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, People’s Republic of China; 4Neuroscience Research Institute, Peking University, Beijing, People’s Republic of China; 5Key Laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Peking University, Beijing, People’s Republic of China; 6Autism Research Center of Peking University Health Science Center, Beijing, People’s Republic of ChinaCorrespondence: Zhiping Zhen; Rong Zhang, Email zzpxt@bnu.edu.cn; zhangrong@bjmu.edu.cnBackground: Autism spectrum disorder (ASD) is a developmental disorder characterized by social behavior deficits and stereotyped behaviors in childhood that lacks satisfactory medical intervention. Early swimming intervention is a noninvasive method combining enriched environment and exercise, which has been proven to improve brain development in young children and to treat neurodevelopmental diseases.Methods: In this study, we tested the autism-like behavior of rats with deletions in exons 11– 21 of the Shank3 gene and evaluated the effect of early swimming intervention (from postnatal day 8 to 60) on the behavior of this animal model of autism. In addition, the transcriptomes of the striatal tissues of wild-type, Shank3 knockout and Shank3 knockout swimming groups rats were analyzed.Results: Shank3 knockout rats exhibit core symptoms of autism, and early swimming improved the social and stereotyped behaviors in this autism rat model. Transcriptomics results revealed that compared to the wild-type group, 291 differentially expressed genes (DEGs) were identified in the striatum of the Shank3 knockout group. Compared to Shank3 knockout group, 534 DEGs were identified in the striatum of Shank3 knockout swimming group. The DEGs annotated by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway shows that the impacts of Shank3 deletion were primarily reflected in synaptic structure, development, morphology, receptor function and signaling, and swimming primarily changed the terms related to the synapses in the striatum of Shank3 knockout rats, including the morphology, structure, composition, development and regulation of synapses.Conclusion: Early swimming intervention can ameliorate behavioral abnormalities caused by Shank3 knockout, by a mechanism that may involve the process of striatal synaptic development and should be further investigated.Keywords: Shank3, autism, early swimming, behavior, transcriptome