PIEZO2 is the underlying mediator for precise magnetic stimulation of PVN to improve autism-like behavior in mice.

Abstract

The precision magnetic stimulation system (pMSS), mediated by superparamagnetic iron oxide nanoparticles (SPIONs), can modulate endogenous oxytocin secretion by targeting the paraventricular nucleus (PVN) and improve autistic-like behavior in mice. In this study, the underlying mechanisms of this system were explored. Our findings demonstrate that pMSS bi-directionally regulates oxytocin secretion, inhibiting secretion at a low frequency (1 Hz) and promoting secretion at a high frequency (10 Hz). Transcriptome screening and replicate validation reveal that 10 Hz-pMSS promotes the expression of mechanosensitive Piezo2 channels on oxytocinergic neurons, increasing neuronal calcium influx and activating oxytocin and PI3K-Akt signaling pathways. Specific knockdown of Piezo2 in PVN blocks the effect of 10 Hz-pMSS, improving autistic-like behavior in mice. Mechanistically, valproic acid-induced autism model mice exhibit low oxytocin secretion and inhibition of neurite growth, and magnetomechanical stimulation by 10 Hz-pMSS can reverse these differences. Thus, 10 Hz-pMSS targeting the PVN rapidly reduces autistic-like behaviors in mice mediated by activation of Piezo2 in the PVN, increased neuronal calcium influx, and alterations in oxytocin secretion and neurite growth.