Hou Shule, Zhang Jifang, Wu Yan, Junmin Chen, Yuyu Huang, He Baihui, Yang Yan, Hong Yuren, Chen Jiarui, Yang Jun, Li Shuna
Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Ear Institute, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Front Mol Neurosci. 2022 Jul 28;15:922665. doi: 10.3389/fnmol.2022.922665. eCollection 2022.
Ribbon synapses are important structures in transmitting auditory signals from the inner hair cells (IHCs) to their corresponding spiral ganglion neurons (SGNs). Over the last few decades, deafness has been primarily attributed to the deterioration of cochlear hair cells rather than ribbon synapses. Hearing dysfunction that cannot be detected by the hearing threshold is defined as hidden hearing loss (HHL). The relationship between ribbon synapses and FGF22 deletion remains unknown. In this study, we used a 6-week-old FGF22 knockout mice model ( ) and mainly focused on alteration in ribbon synapses by applying the auditory brainstem response (ABR) test, the immunofluorescence staining, the patch-clamp recording, and quantitative real-time PCR. In mice, we found the decreased amplitude of ABR wave I, the reduced vesicles of ribbon synapses, and the decreased efficiency of exocytosis, which was suggested by a decrease in the capacitance change. Quantitative real-time PCR revealed that led to dysfunction in ribbon synapses by downregulating SNAP-25 and Gipc3 and upregulating MEF2D expression, which was important for the maintenance of ribbon synapses' function. Our research concluded that FGF22 deletion caused HHL by affecting the function of IHC ribbon synapses and may offer a novel therapeutic target to meet an ever-growing demand for deafness treatment.
带状突触是将听觉信号从内毛细胞（IHC）传递到其相应螺旋神经节神经元（SGN）的重要结构。在过去几十年中，耳聋主要归因于耳蜗毛细胞的退化，而非带状突触。无法通过听力阈值检测到的听力功能障碍被定义为隐匿性听力损失（HHL）。带状突触与FGF22缺失之间的关系仍然未知。在本研究中，我们使用了6周龄的FGF22基因敲除小鼠模型（ ），并主要通过应用听觉脑干反应（ABR）测试、免疫荧光染色、膜片钳记录和定量实时PCR来关注带状突触的变化。在 小鼠中，我们发现ABR波I的振幅降低、带状突触的囊泡减少以及胞吐效率降低，这通过电容变化的减少得到提示。定量实时PCR显示， 通过下调SNAP-25和Gipc3以及上调MEF2D表达导致带状突触功能障碍，而MEF2D表达对维持带状突触的功能很重要。我们的研究得出结论，FGF22缺失通过影响IHC带状突触的功能导致HHL，并可能为满足对耳聋治疗不断增长的需求提供一个新的治疗靶点。
