Presbycusis results from age-related degeneration of the auditory system. D-galactose (D-gal)-induced aging is an ideal and commonly used animal model in aging research. Previous studies demonstrate that administration of D-gal can activate mitochondria-dependent apoptosis in the cochlear stria vascularis. However, D-gal-induced changes to cochlear inner (IHCs) and outer (OHCs) hair cells, spiral ganglion cells (SGCs), and ribbon synapses connecting IHCs and SGCs have not been systematically reported. The current study investigated changes in the numbers of hair cells, SGCs, and ribbon synapses in the mouse model of aging. We found that in comparison to control mice, the numbers of ribbon synapses and their nerve fibers were significantly decreased in D-gal-treated mice, whereas the numbers of OHCs, IHCs, and SGCs were almost unchanged. Moreover, hair cell stereocilia were also not obviously influenced by D-gal administration. Although D-gal-induced aging did not significantly shift the auditory brainstem response (ABR) thresholds in the 8, 16, and 32 kHz frequency bands, the amplitude and latency of the ABR wave I, reflecting ribbon synapse functions, were abnormal in D-gal-treated mice compared to control mice. We also found that 8-hydroxy-2-deoxyguanosine, a marker of oxidative DNA damage, was significantly increased in mitochondria of cochleae from mice exposed to D-gal-induced aging in comparison to control mice. Moreover, D-gal administration increased the levels of H2O2 and mitochondrial 3860-bp common deletion, and decreased superoxide dismutase activity and ATP production in the cochlea. Furthermore, compared with control mice, the protein levels of NADPH oxidase 2 and uncoupling protein 2 were significantly increased in the cochlea of D-gal-treated mice. Taken together, these findings support that the cochlear ribbon synapse is the primary insult site in the early stage of presbycusis, and mitochondrial oxidative damage and subsequent dysfunctions might be responsible for this insult.

中文翻译：

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年龄相关的耳蜗带状突触的侮辱：D-半乳糖诱导的小鼠衰老的早期起因。

老年性耳聋是由与年龄有关的听觉系统退化引起的。D-半乳糖（D-gal）诱导的衰老是衰老研究中一种理想且常用的动物模型。先前的研究表明，D-gal的使用可以激活耳蜗血管纹的线粒体依赖性细胞凋亡。但是，D-gal诱导的耳蜗内（IHC）和外（OHC）毛细胞，螺旋神经节细胞（SGC）以及连接IHC和SGC的带状突触的改变尚未得到系统报道。目前的研究调查了衰老小鼠模型中毛细胞，SGC和带状突触数量的变化。我们发现，与对照小鼠相比，D-gal处理的小鼠中带状突触及其神经纤维的数量明显减少，而OHC，IHC和SGC的数量几乎没有变化。而且，毛细胞立体纤毛也不受D-gal给药的明显影响。尽管D-gal引起的衰老并没有明显改变8、16和32 kHz频带中的听觉脑干反应（ABR）阈值，但D中反射带状突触功能的ABR波I的振幅和潜伏期在D中是异常的-gal治疗的小鼠与对照小鼠相比。我们还发现，与对照小鼠相比，暴露于D-gal诱导衰老的小鼠耳蜗线粒体中的8-羟基-2-脱氧鸟苷（氧化DNA损伤的标志物）显着增加。此外，D-gal给药增加了H2O2和线粒体3860bp常见缺失的水平，并降低了耳蜗中的超氧化物歧化酶活性和ATP的产生。此外，与对照组小鼠相比，D-gal处理的小鼠的耳蜗中NADPH氧化酶2和解偶联蛋白2的蛋白水平显着增加。综上所述，这些发现支持耳蜗丝带突触是老年性耳聋早期的主要损伤部位，线粒体的氧化损伤和随后的功能障碍可能是造成该损伤的原因。