Role of purinergic receptors 2X3 on type II spiral ganglion neurons in the enhancement of medial olivocochlear reflex in mice after long-term noise exposure

Abstract

Objective: This study aimed to elucidate the role of P2X3 receptors on type II spiral ganglion neurons (SGNs) in mediating the enhancement of the medial olivocochlear (MOC) reflex following long-term noise exposure.

Methods: We utilized four groups of male CBA/Ca mice: control, ouabain, ouabain noise, and ouabain noise + AF-353. The ouabain group received local cochlear application of ouabain to selectively induce apoptosis of type I SGNs. The ouabain noise group was then exposed to moderate noise [80 dB sound pressure level (SPL)] for 6 h daily over 4 weeks, while the ouabain noise + AF-353 group received the P2X3 receptor blocker AF-353 before noise sessions. Auditory brainstem responses (ABRs) and distortion product otoacoustic emissions (DPOAEs) were measured to assess hearing. The MOC reflex was evaluated via contralateral and ipsilateral suppression of DPOAEs. Immunofluorescence visualized P2X3 receptor expression.

Results: Ouabain-treated mice exposed to noise displayed a significantly enhanced MOC reflex, which was attenuated by AF-353. ABR thresholds were elevated and wave I amplitude was reduced, suggesting hearing impairment, whereas DPOAE thresholds were unchanged. Immunofluorescence indicated a marked upregulation of P2X3 receptors in the cochlea's middle turn after noise exposure, an effect decreased by AF-353.

Conclusion: The enhanced MOC reflex induced by long-term moderate noise exposure is mediated by the upregulation of P2X3 receptors on type II SGNs. The selective ablation of type I SGNs confirms the pivotal role of type II SGNs in this adaptive neural plasticity.

Keywords: P2X3; hearing functions; long-term moderate noise; medial olivocochlear reflex; type II spiral ganglion neurons.