Effect of regulating Piezo2 expression in DRG on core phenotype, S1 and mPFC neuron functions in ASD mouse model

Background: Tactile overreaction (TOR) in the symptoms of autism spectrum disorder (ASD) has attracted attention because of its high incidence and potential influence on the core phenotype. However, the possible causes of TOR are unclear. Piezo2 is a mechanically gated ion channel that mainly mediates low-threshold touch. But there is no research to prove whether it is related to the tactile symptoms of ASD. In this study, we investigated the expression of Piezo2 in peripheral nervous system of BTBR in ASD model mice, and whether Piezo2 inhibitor GsMTx4 can alleviate the symptoms of ASD such as TOR and social injury, and evaluated the effects on the function of neurons in primary somatosensory cortex (S1) and medial prefrontal cortex (mPFC). At the same time, we further explored whether soft touch stimulation, a non-invasive intervention method, can achieve similar effects as GsMTx4 administration. Results Piezo2 was overexpressed in the dorsal root ganglion (DRG) of BTBR mice than that in wild-type C57BL/6(C57) mice, accompanied by TOR of hairless skin on the sole. However, this overexpression was not found in the trigeminal ganglion (TG), and no obvious abnormal response of the face to stimulation was observed. Starting from the 28th day after BTBR was born, administration of GsMTx4 for 3 days alleviated the TOR, social deficits, and repetitive behavior in BTBR. Surprisingly, neuron overactivation in the S1 and mPFC during social activities reduced, while dendritic spine density in mPFC increased. We further found that chronic soft touch also could improve behavior and central nervous system function, accompanied by the decrease of Piezo2 overexpression in the DRG of BTBR. Conclusion GsMTx4 administration and soft tactile stimulation can effectively inhibit the over-expression of Piezo2 in DRG of BTBR mice, alleviate a series of ASD symptoms such as TOR and social defects, and improve the functions of S1 and mPFC cortical neurons.