Swimming Improves Autistic Behavior in Shank3 Knockout Rats by Modulating Synaptic Structural Plasticity in Striatum

Objective: Autism spectrum disorder(ASD) typically manifests during early childhood, with its behavioral deficits intricately linked to striatal function. Early childhood represents a crucial stage in brain development, and swimming has proven to be an effective exercise regimen for enhancing synaptic plasticity in the brain. In this study, we explored whether early swimming could influence the synaptic structural plasticity of striatal synapses in Shank3 knockout ASD rats and potentially ameliorate ASDlike behaviors closely associated with striatal function. Methods: Male Shank3 knockout SD rats were randomly divided into gene knockout control group(KC) and gene knockout swimming group(KS). Wild type rats in the same litter were randomly divided into wild type control group(WC) and wild type swimming group(WS). The KS and WS groups were conducted swimming intervention for 8 weeks from postnatal day 8, and the behavioral tests including self-grooming, open field experiment, maximum grasping force experiment and rod-turning experiment were performed after intervention. After 24 h of behavioral test, the Golgi staining were performed in striatum to observe the dendritic morphology of medium spiny neurons(MSNs). The expressions of excitatory postsynaptic scaffold protein and glutamate and γ-aminobutyric acid receptors were detected with Western blot in the postsynaptic dense part(PSD) of striatum. Results: The early life swimming intervention significantly improved the stereotyped behavior and motor ability, but not anxiety symptom, in Shank3 knockout rats. The total length, number of branches and dendritic spine density of MSNs in striatum were significantly decreased in Shank3 knockout rats, and early swimming rescued these changes in dendritic morphology. The expressions of PSD95 and Homer1 in the postsynaptic dense part of striatum were significantly decreased, and the receptor protein expressions of GluA1, GluA2, NR1, NR2A and NR2B were significantly decreased. In addition, Early swimming intervention increased the expressions of PSD95 and GluA1, GluA2, NR2A and NR2B in Shank3 knockout rats. Conclusions:Shank3 knockout rats show impaired dendritic development, decreased expression of excitatory postsynaptic receptors, and stereotyped behavior and motor dysfunction associated with abnormal striatum function. Commencing swimming intervention at an early stage enhances the proliferation of striatal dendritic branches, increases total dendritic length, and elevates dendritic spine density. Furthermore, it leads to an upregulation in the expression of certain excitatory postsynaptic receptor proteins. Consequently,this intervention effectively influences synaptic structural plasticity and mitigates the behavioral abnormalities induced by Shank3knockout in rats.