Yang Zi-Jing, Zhao Chun-Li, Liang Wen-Qi, Chen Zhong-Rui, Du Zheng-De, Gong Shu-Sheng
Department of Otolaryngology Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University Beijing 100050, China.
Clinical Center for Hearing Loss, Capital Medical University Beijing 100050, China.
Am J Transl Res. 2024 Jan 15;16(1):272-284. doi: 10.62347/EVDE9449. eCollection 2024.
Evidence suggests that damage to the ribbon synapses (RS) may be the main cause of auditory dysfunction in noise-induced hearing loss (NIHL). Oxidative stress is implicated in the pathophysiology of synaptic damage. However, the relationship between oxidative stress and RS damage in NIHL remains unclear. To investigate the hypothesis that noise-induced oxidative stress is a key factor in synaptic damage within the inner ear, we conducted a study using mice subjected to single or repeated noise exposure (NE). We assessed auditory function using auditory brainstem response (ABR) test and examined cochlear morphology by immunofluorescence staining. The results showed that mice that experienced a single NE exhibited a threshold shift and recovered within two weeks. The ABR wave I latencies were prolonged, and the amplitudes decreased, suggesting RS dysfunction. These changes were also demonstrated by the loss of RS as evidenced by immunofluorescence staining. However, we observed threshold shifts that did not return to baseline levels following secondary NE. Additionally, ABR wave I latencies and amplitudes exhibited notable changes. Immunofluorescence staining indicated not only severe damage to RS but also loss of outer hair cells. We also noted decreased T-AOC, ATP, and mitochondrial membrane potential levels, alongside increased hydrogen peroxide concentrations post-NE. Furthermore, the expression levels of 4-HNE and 8-OHdG in the cochlea were notably elevated. Collectively, our findings suggest that the production of reactive oxygen species leads to oxidative damage in the cochlea. This mitochondrial dysfunction consequently contributes to the loss of RS, precipitating an early onset of NIHL.
有证据表明，带状突触（RS）损伤可能是噪声性听力损失（NIHL）中听觉功能障碍的主要原因。氧化应激与突触损伤的病理生理学有关。然而，NIHL中氧化应激与RS损伤之间的关系仍不清楚。为了研究噪声诱导的氧化应激是内耳突触损伤的关键因素这一假说，我们使用单次或重复噪声暴露（NE）的小鼠进行了一项研究。我们使用听觉脑干反应（ABR）测试评估听觉功能，并通过免疫荧光染色检查耳蜗形态。结果表明，经历单次NE的小鼠出现阈值偏移，并在两周内恢复。ABR波I潜伏期延长，振幅降低，提示RS功能障碍。免疫荧光染色证实RS丢失也证明了这些变化。然而，我们观察到二次NE后阈值偏移未恢复到基线水平。此外，ABR波I潜伏期和振幅出现显著变化。免疫荧光染色不仅表明RS严重受损，还表明外毛细胞丢失。我们还注意到NE后总抗氧化能力（T-AOC）、三磷酸腺苷（ATP）和线粒体膜电位水平降低，而过氧化氢浓度升高。此外，耳蜗中4-羟基壬烯醛（4-HNE）和8-羟基脱氧鸟苷（8-OHdG）的表达水平显著升高。总的来说，我们的研究结果表明，活性氧的产生导致耳蜗氧化损伤。这种线粒体功能障碍进而导致RS丢失，促使NIHL早期发病。
