FGF13 prevents age-related hearing loss by protecting spiral ganglion neurons and ribbon synapses from injury.

IF 6.1 2区生物学 Q1 CELL BIOLOGY

Cell Death Discovery Pub Date : 2025-07-05 DOI:10.1038/s41420-025-02607-5

Huan Yin, Huan Cao, Jianwang Yang, Tao Liu, Qi Li, Mengxiao Liu, Baoshan Wang

{"title":"FGF13 prevents age-related hearing loss by protecting spiral ganglion neurons and ribbon synapses from injury.","authors":"Huan Yin, Huan Cao, Jianwang Yang, Tao Liu, Qi Li, Mengxiao Liu, Baoshan Wang","doi":"10.1038/s41420-025-02607-5","DOIUrl":null,"url":null,"abstract":"<p><p>Age-related hearing loss (ARHL) is the most common sensorineural hearing loss, and the dysfunction of spiral ganglion neurons (SGNs) and ribbon synapses plays a crucial role in the pathogenesis. The fibroblast growth factor 13 (FGF13) is considered to be associated with neuronal survival and synaptic transmission. However, whether FGF13 is involved in degeneration of SGNs and ribbon synapses, the typical changes of ARHL, is still unknown. Firstly, the expression of FGF13 mRNA and protein, was all dramatically decreased in the SGNs of aged mice, accompanied by impaired SGNs and ribbon synapses. More importantly, specific upregulation of FGF13 in SGNs significantly reduced hearing threshold, improved wave I amplitude, and alleviated loss of SGNs as well as ribbon synapses. Furthermore, the proteomic analysis and verification results suggested that the decrease of FGF13 induced the loss of SGNs and ribbon synapses partly by regulating the ORC1. Taken together, our data revealed that FGF13 might protect SGNs and ribbon synapses by regulating the expression of ORC1, which could provide a new idea and targets for the prevention and treatment of ARHL.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"307"},"PeriodicalIF":6.1000,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12228769/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Death Discovery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41420-025-02607-5","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Age-related hearing loss (ARHL) is the most common sensorineural hearing loss, and the dysfunction of spiral ganglion neurons (SGNs) and ribbon synapses plays a crucial role in the pathogenesis. The fibroblast growth factor 13 (FGF13) is considered to be associated with neuronal survival and synaptic transmission. However, whether FGF13 is involved in degeneration of SGNs and ribbon synapses, the typical changes of ARHL, is still unknown. Firstly, the expression of FGF13 mRNA and protein, was all dramatically decreased in the SGNs of aged mice, accompanied by impaired SGNs and ribbon synapses. More importantly, specific upregulation of FGF13 in SGNs significantly reduced hearing threshold, improved wave I amplitude, and alleviated loss of SGNs as well as ribbon synapses. Furthermore, the proteomic analysis and verification results suggested that the decrease of FGF13 induced the loss of SGNs and ribbon synapses partly by regulating the ORC1. Taken together, our data revealed that FGF13 might protect SGNs and ribbon synapses by regulating the expression of ORC1, which could provide a new idea and targets for the prevention and treatment of ARHL.

查看原文本刊更多论文

FGF13通过保护螺旋神经节神经元和带状突触免受损伤来预防与年龄相关的听力损失。

年龄相关性听力损失（Age-related hearing loss， ARHL）是最常见的感音神经性听力损失，螺旋神经节神经元（sgn）和带状突触功能障碍在其发病机制中起着至关重要的作用。成纤维细胞生长因子13 （FGF13）被认为与神经元存活和突触传递有关。然而，FGF13是否参与了sgn和带状突触的变性，这是ARHL的典型变化，目前尚不清楚。首先，老龄小鼠sgn中FGF13 mRNA和蛋白的表达均显著降低，sgn和带状突触受损。更重要的是，在sgn中特异性上调FGF13可显著降低听力阈值，提高波I振幅，减轻sgn和带状突触的损失。此外，蛋白质组学分析和验证结果表明，FGF13的减少部分通过调节ORC1来诱导sgn和带状突触的丢失。综上所述，我们的数据显示FGF13可能通过调节ORC1的表达来保护sgn和带状突触，这可能为ARHL的预防和治疗提供新的思路和靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Cell Death Discovery Biochemistry, Genetics and Molecular Biology-Cell Biology

CiteScore

8.30

自引率

1.40%

发文量

468

审稿时长

9 weeks

期刊介绍： Cell Death Discovery is a multidisciplinary, international, online-only, open access journal, dedicated to publishing research at the intersection of medicine with biochemistry, pharmacology, immunology, cell biology and cell death, provided it is scientifically sound. The unrestricted access to research findings in Cell Death Discovery will foster a dynamic and highly productive dialogue between basic scientists and clinicians, as well as researchers in industry with a focus on cancer, neurobiology and inflammation research. As an official journal of the Cell Death Differentiation Association (ADMC), Cell Death Discovery will build upon the success of Cell Death & Differentiation and Cell Death & Disease in publishing important peer-reviewed original research, timely reviews and editorial commentary. Cell Death Discovery is committed to increasing the reproducibility of research. To this end, in conjunction with its sister journals Cell Death & Differentiation and Cell Death & Disease, Cell Death Discovery provides a unique forum for scientists as well as clinicians and members of the pharmaceutical and biotechnical industry. It is committed to the rapid publication of high quality original papers that relate to these subjects, together with topical, usually solicited, reviews, editorial correspondence and occasional commentaries on controversial and scientifically informative issues.