Whisker stimulation alleviate ASD behavior of BTBR mice by regulating Piezo2 expression in DRG and neuron function in S1 and mPFC

Abstract Background: Individuals with autism spectrum disorder (ASD) commonly experience sensory abnormalities, including tactile sensation, in addition to social and repetitive restrictive behavior. This study aimed to evaluate the tactile response characteristics of children with ASD and its correlation with core phenotypes, as well as investigate the role of Piezo2 mechanically sensitive ion channels in the tactile behavior of BTBR mice. Additionally, the study explored the effects of tactile intervention on the neural function of key sensory and social brain regions in mouse model. Methods: A population questionnaire survey was conducted to compare the scores of the Short Sensory Profile (SSP) between children with ASD and typically developing children, and analyze the correlation between SSP and social response scales (SRS) and other clinical diagnostic tools in the ASD group. Behavioral tests such as Von Frey, three-chamber social test, open field, self-grooming, and Morris water maze were performed on BTBR and C57BL/6 mice to evaluate tactile and ASD characteristics. Expression of Piezo2 in the dorsal root ganglion (DRG), and the neural function in the mPFC/S1 brain region were detected in the whisker intervention group and the non-intervention group. Results: Children with ASD showed significant tactile sensitivity compared to typically developing children, and increased tactile abnormality was associated with greater social abnormality. In animal experiments, BTBR mice with tactile overreaction exhibited over-expression of Piezo2 protein and mRNA in the DRG. Tactile intervention relieved tactile sensitivity and ASD symptoms, and decreased the over-expression of Piezo2. Additionally, there was a significant increase in dendritic spine density in S1 and mPFC brain regions, and a decrease in the level of c-fos. Limitations: The causal relationship between ASD tactile sensitivity and social injury should be further clarified in future research. And clarify the neural mechanism of mild tactile stimulation affecting ASD symptoms.