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

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单位: [1]Department of Otolaryngology-Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China
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关键词: Aging-related hearing loss cochlea endocytosis inner hair cells ribbon synapse

摘要:
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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出版当年[2019]版:
大类 | 3 区 医学
小类 | 3 区 医学:研究与实验 4 区 肿瘤学
最新[2025]版:
大类 | 4 区 医学
小类 | 4 区 医学:研究与实验 4 区 肿瘤学
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出版当年[2018]版:
Q2 ONCOLOGY Q2 MEDICINE, RESEARCH & EXPERIMENTAL
最新[2023]版:
Q3 MEDICINE, RESEARCH & EXPERIMENTAL Q4 ONCOLOGY

影响因子: 最新[2023版] 最新五年平均[2021-2025] 出版当年[2018版] 出版当年五年平均[2014-2018] 出版前一年[2017版] 出版后一年[2019版]

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第一作者单位: [1]Department of Otolaryngology-Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China
通讯作者:
通讯机构: [1]Department of Otolaryngology-Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China [*1]Department of Otolaryngology-Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, 95 Yong’an Road, Beijing 100050, China.
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