FGF22 deletion causes hidden hearing loss by affecting the function of inner hair cell ribbon synapses.
FGF22 deletion causes hidden hearing loss by affecting the function of inner hair cell ribbon synapses.
复制标题
FGF22 缺失通过影响内毛细胞带状突触的功能导致隐性听力损失
DOI：
10.3389/fnmol.2022.922665
复制
发表时间：
2022
影响因子：
4.8
通讯作者：
Li, Shuna
中科院分区：
文献类型：
--
作者：
Hou, Shule;Zhang, Jifang;Yan Wu;Chen Junmin;Huang Yuyu;He, Baihui;Yan Yang;Hong, Yuren;Chen, Jiarui;Jun Yang;Li, Shuna
带状突触是内毛细胞向螺旋神经节神经元传递听觉信号的重要结构。在过去的几十年里，耳聋主要归因于耳蜗毛细胞的退化，而不是带状突触。听力阈值无法检测到的听力障碍被定义为隐性听力损失（HHL）。带状突触和FGF 22缺失之间的关系仍然未知。本研究采用6周龄FGF 22基因敲除小鼠模型（Fgf 22-/-），通过听性脑干反应（ABR）测试、免疫荧光染色、膜片钳记录和实时定量PCR等方法，主要研究带状突触的变化。在Fgf 22-/-小鼠中，我们发现ABR波I的幅度降低，带状突触的小泡减少，胞吐效率降低，这是由电容变化的减少所暗示的。实时定量PCR结果显示，Fgf 22-/-通过下调SNAP-25和Gipc 3的表达，上调MEF 2D的表达，导致带状突触功能障碍，这对维持带状突触的功能具有重要意义。我们的研究得出结论，FGF 22缺失通过影响IHC带状突触的功能引起HHL，并可能提供一种新的治疗靶点，以满足日益增长的耳聋治疗需求。
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 (Fgf22–/–) 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 Fgf22–/– 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 Fgf22–/– 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.
登录
查看更多内容
影响因子：
2.9
作者：
Ghelani T;Sigrist SJ
通讯作者：
Sigrist SJ
影响因子：
4.6
作者：
Jan, Taha Adnan;Chai, Renjie;Cheng, Alan Gi-Lun
通讯作者：
Cheng, Alan Gi-Lun
斑马鱼神经丘毛细胞再生需要 Myc 和 Fgf
影响因子：
3.7
作者：
Lee SG;Huang M;Obholzer ND;Sun S;Li W;Petrillo M;Dai P;Zhou Y;Cotanche DA;Megason SG;Li H;Chen ZY
通讯作者：
Chen ZY
影响因子：
11.4
作者：
Jacobi, Anne;Loy, Kristina;Bareyre, Florence M.
通讯作者：
Bareyre, Florence M.
影响因子：
5.3
作者：
Haque, Khujista;Pandey, Atul K.;Puligilla, Chandrakala
通讯作者：
Puligilla, Chandrakala