听力损失与帕金森病：来自人类与动物研究的见解

文献信息

中文摘要

背景： 听力损失（HL）与帕金森病（PD）的关联日益受到关注，但二者之间的流行病学关联及潜在生物学机制仍不清楚。本研究旨在探讨HL与PD之间的关联，并探索听觉剥夺与PD相关病理之间的潜在生物学联系。
方法： 采用多因素logistic回归分析美国国家健康与营养调查（NHANES）和中国健康与养老追踪调查（CHARLS）的数据，并在倾向评分匹配样本中进行敏感性分析，其中NHANES包含70对匹配样本，CHARLS包含171对匹配样本。同时，通过听骨链中断建立听觉剥夺模型，而PD相关病理通过每日给予MPTP、分三个7天治疗区组（共21次注射）建模，各区组之间设有48小时无药物评估间隔。听觉剥夺通过听性脑干反应确认。运动功能采用旷场实验和转棒实验评估，多巴胺能神经元丢失通过免疫荧光评估。进行纹状体RNA测序，并与GSE205450数据集整合，以探索潜在分子机制。
结果： 在NHANES（OR，1.79；95% CI，1.24-2.58）和CHARLS（OR，1.42；95% CI，1.01-2.01）中，自我报告的听力障碍均与更高的PD患病几率相关。在倾向评分匹配分析中，该关联在NHANES（70对匹配样本）和CHARLS（171对匹配样本）中仍然显著。在动物实验中，运动表现和TH阳性多巴胺能神经元计数均观察到显著的HL × MPTP交互作用，HL + MPTP小鼠的结局较仅MPTP小鼠更差。转录组分析确定Adcyap1为听觉剥夺与PD相关改变之间的跨物种候选分子联系。
结论： 在基于人群的分析中，自我报告的听力障碍与PD相关，而实验研究结果支持听觉剥夺与更严重的MPTP相关运动和 dopaminergic 异常之间存在潜在关系。

英文摘要

BACKGROUND: Hearing 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.
METHODS: Data 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.
RESULTS: Self-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.
CONCLUSIONS: Self-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.