It is widely accepted that even a single acute noise exposure at moderate intensity that induces temporary threshold shift (TTS) can result in permanent loss of ribbon synapses between inner hair cells and afferents. However, effects of repeated or chronic noise exposures on the cochlear synapses especially medial olivocochlear (MOC) efferent synapses remain elusive. Based on a weeklong repeated exposure model of bandwidth noise over 2-20 kHz for 2 hours at seven intensities (88 to 106 dB SPL with 3 dB increment per gradient) on C57BL/6J mice, we attempted to explore the dose-response mechanism of prolonged noise-induced audiological dysfunction and cochlear synaptic degeneration. In our results, mice repeatedly exposed to relatively low-intensity noise (88, 91, and 94 dB SPL) showed few changes on auditory brainstem response (ABR), ribbon synapses, or MOC efferent synapses. Notably, repeated moderate-intensity noise exposures (97 and 100 dB SPL) not only caused hearing threshold shifts and the inner hair cell ribbon synaptopathy but also impaired MOC efferent synapses, which might contribute to complex patterns of damages on cochlear function and morphology. However, repeated high-intensity (103 and 106 dB SPL) noise exposures induced PTSs mainly accompanied by damages on cochlear amplifier function of outer hair cells and the inner hair cell ribbon synaptopathy, rather than the MOC efferent synaptic degeneration. Moreover, we observed a frequency-dependent vulnerability of the repeated acoustic trauma-induced cochlear synaptic degeneration. This study provides a sight into the hypothesis that noise-induced cochlear synaptic degeneration involves both afferent (ribbon synapses) and efferent (MOC terminals) pathology. The pattern of dose-dependent pathological changes induced by repeated noise exposure at various intensities provides a possible explanation for the complicated cochlear synaptic degeneration in humans. The underlying mechanisms remain to be studied in the future.

中文翻译：

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重复噪声暴露诱导 C57BL/6J 小鼠耳蜗突触变性的剂量依赖性模式

人们普遍认为，即使是中等强度的单一急性噪声暴露也会导致暂时阈值偏移 (TTS)，从而导致内毛细胞和传入细胞之间的带状突触永久丧失。然而，重复或慢性噪声暴露对耳蜗突触，尤其是内侧橄榄耳蜗 (MOC) 传出突触的影响仍然难以捉摸。基于对 C57BL/6J 小鼠在 7 个强度（88 到 106 dB SPL，每个梯度增量 3 dB）下 2-20 kHz 带宽噪声持续 2 小时的为期一周的重复暴露模型，我们试图探索 C57BL/6J 小鼠的剂量反应机制。长期噪声引起的听力功能障碍和耳蜗突触变性。在我们的结果中，反复暴露于相对低强度噪声（88、91 和 94 dB SPL）的小鼠在听觉脑干反应（ABR）方面几乎没有变化，带状突触，或 MOC 传出突触。值得注意的是，重复的中等强度噪声暴露（97 和 100 dB SPL）不仅会导致听力阈值变化和内毛细胞带状突触病变，还会损害 MOC 传出突触，这可能导致耳蜗功能和形态的复杂损害模式。然而，反复高强度（103 和 106 dB SPL）噪声暴露诱发的 PTS 主要伴有外毛细胞和内毛细胞带状突触的耳蜗放大器功能损伤，而不是 MOC 传出突触变性。此外，我们观察到反复声外伤引起的耳蜗突触变性的频率依赖性脆弱性。这项研究提供了一个假设，即噪声引起的耳蜗突触变性涉及传入（带状突触）和传出（MOC 终端）病理学。由不同强度的重复噪声暴露引起的剂量依赖性病理变化模式为人类复杂的耳蜗突触变性提供了可能的解释。其潜在机制仍有待未来研究。