Hearing impairment in Parkinson's disease models: Possible relation with changes in cochlear efferent fibers

Hearing impairments, as a prevalent and debilitating non-motor symptom of Parkinson's disease (PD), remain unclear in mechanisms. In this work, we established PD mouse and rat models by using 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine (6-OHDA), respectively, and investigated their hearing functions and potential mechanisms through auditory brainstem response (ABR), distortion product otoacoustic Emissions (DPOAE), noise exposure, immunofluorescence labeling, volumetric measurement, and colocalization analysis. In MPTP-induced PD mice, we observed significant cholinergic fibers decompensation, heterogeneous dopaminergic fibers damage of cochlear efferent fibers, and adrenergic sympathetic fibers marked loss in the osseous spiral lamina (OSL), corresponding to insignificant cochlear hair cells, ribbon synapse alteration, and auditory sensitivity injury. While in 6-OHDA-induced PD rats, asymmetric alterations in cochlear cholinergic, dopaminergic fibers were found, accompanied by inconsistent adrenergic changes in the OSL, which matched unilateral hair cells, ribbon synapse damage, and hearing loss. Overall, findings from this work indicate that pathological alterations in the cochlea of PD mice and rats, particularly in efferent fibers, may be closely relevant to peripheral hearing alterations.