Loss of cochlear ribbon synapses in the early stage of aging causes initial hearing impairment.

Loss of cochlear ribbon synapses in the early stage of aging causes initial hearing impairment.
复制标题

衰老早期阶段耳蜗带突触的丧失会导致最初的听力障碍。

DOI:
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发表时间:
2020
期刊:
Am J Transl Res
影响因子:
--
通讯作者:
Shusheng Gong
Shusheng Gong
中科院分区:
其他
文献类型:
--
作者:
Wei Xiong;Shukui Yu;Ke Liu;Shusheng Gong

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相似文献

听力损失可能会随着年龄的增长而发生。然而,关于哪种耳蜗组件最容易受到老化损伤以及导致与年龄相关的听力损失的病理事件的影响,仍然存在争议。本研究采用C57 BL/6 J小鼠模拟衰老过程,检测了不同衰老阶段(1、2、4、6个月[M])小鼠的听性脑干反应(ABR)阈值。4 M的寿命被认为是衰老的早期阶段。免疫组化结合激光共聚焦显微镜技术鉴定耳蜗带状突触的标记物RIBEYE/CtBP 2,并对突触带进行定量分析。以ABR波Ⅰ的振幅变化来评价带状突触的功能。此外,还使用荧光标记染料FM 1 -43检测内毛细胞的内吞作用。我们发现,带状突触的丧失在衰老早期先于毛细胞或听神经的丧失,是衰老的初始病理变化。此外,带状突触的丧失,包括突触的数量和功能,被发现对应于跨频率的听阈的升高。此外,内毛细胞的内吞功能的显着减少,在衰老的早期阶段被确定。因此,我们的研究表明,耳蜗带状突触的减少发生在衰老的早期阶段,可能是导致听力损失的原因。
Hearing loss can occur with aging. However, there remains debate about which cochlear component is the most susceptible to aging insult and the consequent pathological events responsible for age-related hearing loss. In this study, we used C57BL/6J mice to mimic the process of aging, and the auditory brainstem response (ABR) thresholds of aging mice were examined at different stages of aging (1, 2, 4, and 6 months [M]). The lifespan of 4 M was considered to be the early stage of aging. Immunostaining combined with laser confocal microscopy was employed to identify RIBEYE/CtBP2, a marker of cochlear ribbon synapses, and a quantitative analysis of the synaptic ribbon was carried out. The function of the ribbon synapse was estimated by amplitude alterations of ABR wave I. Furthermore, endocytosis of the inner hair cells was also detected using the fluorescence labeling dye FM1-43. We found that the loss of ribbon synapses in the early stage of aging occurred prior to hair cell or auditory nerve loss and was the initial pathological change. Additionally, the loss of ribbon synapses, including the quantity and function of synapses, was found to correspond to the elevations of the hearing threshold across frequencies. Moreover, a significant reduction in the endocytosis function of the inner hair cells was identified in the early stage of aging. Therefore, our study indicated that the reduction of cochlear ribbon synapses occurred at an early stage of aging and could be responsible for the consequent hearing loss.
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