Effects of Treadmill Exercise on Autistic Behavior and Prefrontal Cortical SHANK Receptors in Autism Spectrum Disorder Model Mice

Abstract

PURPOSE: The first aim of this study is to change autistic behavior in Shank3B Knock-Out (KO) mice through treadmill exercise (TD), and the second aim is to alter SHANK protein receptors in the prefrontal cortex (PFC) of mice through TD.METHODS: Male mice were divided into Control (11-week-old, n=8), Control+TD (n=8), Shank3B KO (n=8), and Shank3B KO+TD (n=8). Control and Shank3B KO mice were exercised using TD for 2 weeks for 30 minutes each to observe the effects of exercise.RESULTS: Compared to the control group (C57BL/6J), Shank3B KO mice showed excessive self-grooming behavior; however, TD reduced repetitive behavior (<i>p</i><.05). The effect of TD was also seen in the behavior of Shank3B KO mice evaluated by measuring social interaction time using the two-chamber social behavior test and socio-sexual behavior test (<i>p</i><.05 compared to control). Differences were found in C57BL/6J and Shank3B KO mice by assessing proteins such as GluR2, Homer1, phosphorylated GSK-3α/β, and phosphorylated Akt1 in the PFC. The results suggested that TD yielded better outcomes in Shank3B KO+TD mice than in Shank3B KO mice.CONCLUSIONS: TD positively affected behavioral changes in repetitive behavior and social interaction defects in autism spectrum disorder (ASD) model mice. Alterations were also observed in the SHANK glutamate receptor and SHANK sub-signal transporter phosphorylation protein. This suggests that TD is an effective way to improve autistic behavior in ASD. However, further research is necessary to clarify the effects of TD by studying the underlying mechanisms and changes in SHANK proteins and other factors.