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.