PDF(Pubmed)
Abstract：
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.
摘要：
有证据表明，带状突触（RS）的损伤可能是噪声引起的听力损失（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损伤的关系尚不清楚。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的假设，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，经历单一NE的小鼠表现出阈值偏移，并在两周内恢复。ABR波I潜伏期延长,振幅减小，提示RS功能障碍。如免疫荧光染色所证明的,RS的丢失也证明了这些变化。然而,我们观察到继发性NE后阈值变化未恢复至基线水平.此外,ABR波I的潜伏期和振幅表现出显着变化。免疫荧光染色不仅表明RS严重受损，而且外毛细胞丢失。我们还注意到T-AOC下降，ATP,和线粒体膜电位水平，随着过氧化氢浓度的增加，后NE。此外，4-HNE和8-OHdG在耳蜗中的表达水平显著升高。总的来说，我们的发现表明，活性氧的产生会导致耳蜗的氧化损伤。这种线粒体功能障碍因此导致RS的丢失，沉淀NIHL的早期发作。
