FGF22 deletion causes hidden hearing loss by affecting the function of inner hair cell ribbon synapses

Shule Hou; Shule Hou; Shule Hou; Jifang Zhang; Jifang Zhang; Jifang Zhang; Yan Wu; Yan Wu; Yan Wu; Chen Junmin; Chen Junmin; Chen Junmin; Huang Yuyu; Huang Yuyu; Huang Yuyu; Baihui He; Baihui He; Baihui He; Yan Yang; Yuren Hong; Jiarui Chen; Jun Yang; Jun Yang; Jun Yang; Shuna Li; Shuna Li; Shuna Li

doi:10.3389/fnmol.2022.922665

Frontiers in Molecular Neuroscience (Jul 2022)

FGF22 deletion causes hidden hearing loss by affecting the function of inner hair cell ribbon synapses

Shule Hou,
Shule Hou,
Shule Hou,
Jifang Zhang,
Jifang Zhang,
Jifang Zhang,
Yan Wu,
Yan Wu,
Yan Wu,
Chen Junmin,
Chen Junmin,
Chen Junmin,
Huang Yuyu,
Huang Yuyu,
Huang Yuyu,
Baihui He,
Baihui He,
Baihui He,
Yan Yang,
Yuren Hong,
Jiarui Chen,
Jun Yang,
Jun Yang,
Jun Yang,
Shuna Li,
Shuna Li,
Shuna Li

Affiliations

Shule Hou: Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Shule Hou: Ear Institute, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Shule Hou: Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China
Jifang Zhang: Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Jifang Zhang: Ear Institute, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Jifang Zhang: Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China
Yan Wu: Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Yan Wu: Ear Institute, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Yan Wu: Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China
Chen Junmin: Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Chen Junmin: Ear Institute, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Chen Junmin: Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China
Huang Yuyu: Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Huang Yuyu: Ear Institute, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Huang Yuyu: Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China
Baihui He: Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Baihui He: Ear Institute, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Baihui He: Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China
Yan Yang: Liaoning Medical Device Test Institute, Shenyang, China
Yuren Hong: Laboratory of Electron Microscope Center, Shanghai Medical College, Fudan University, Shanghai, China
Jiarui Chen: Department of Otorhinolaryngology-Head and Neck Surgery, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Shanghai, China
Jun Yang: Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Jun Yang: Ear Institute, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Jun Yang: Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China
Shuna Li: Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Shuna Li: Ear Institute, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Shuna Li: Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China

DOI: https://doi.org/10.3389/fnmol.2022.922665
Journal volume & issue: Vol. 15

Abstract

Read online

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.

Published in Frontiers in Molecular Neuroscience

ISSN: 1662-5099 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.frontiersin.org/journals/molecular-neuroscience

About the journal

Abstract

Keywords