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BackgroundHearing loss (HL) has been increasingly implicated in Parkinson's disease (PD), but the epidemiological association between them and the underlying biological mechanisms remain unclear. This study aimed to investigate the association between HL and PD and to explore potential biological links between auditory deprivation and PD-related pathology.MethodsData from the National Health and Nutrition Examination Survey (NHANES) and the China Health and Retirement Longitudinal Study (CHARLS) were analyzed using multivariable logistic regression, with sensitivity analyses performed in propensity score-matched samples comprising 70 matched pairs in NHANES and 171 matched pairs in CHARLS. In parallel, an auditory-deprivation model was established by ossicular chain interruption, while PD-related pathology was modeled by MPTP administration once daily in three 7-day treatment blocks (21 injections in total), with 48-h drug-free assessment intervals between blocks. Auditory deprivation was confirmed by auditory brainstem response. Motor function was assessed using the open field and rotarod tests, and dopaminergic neuron loss was evaluated by immunofluorescence. Striatal RNA sequencing, integrated with the GSE205450 dataset, was conducted to explore potential molecular mechanisms.ResultsSelf-reported hearing impairment was associated with higher odds of PD in both NHANES (OR, 1.79; 95% CI, 1.24-2.58) and CHARLS (OR, 1.42; 95% CI, 1.01-2.01). In propensity score-matched analyses, the association remained significant in NHANES (70 matched pairs) and CHARLS (171 matched pairs). In animal experiments, significant HL × MPTP interactions were observed for motor performance and TH-positive dopaminergic neuron counts, with poorer outcomes in HL + MPTP mice than in MPTP-only mice. Transcriptomic analysis identified Adcyap1 as a cross-species candidate molecular link between auditory deprivation and PD-related alterations.ConclusionsSelf-reported hearing impairment was associated with PD in the population-based analyses, while experimental findings support a potential relationship between auditory deprivation and greater MPTP-related motor and dopaminergic abnormalities.
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