Development of preventive and therapeutic methods for cochlear synaptopathy

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K18792
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Tohoku University
• Principal Investigator: Suzuki Jun 東北大学, 大学病院, 講師 (80735895)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: Cochlear synaptopathy / ミトコンドリア障害 / グルタミン酸毒性 / 抗酸化作用 / 音響性聴覚障害 / 騒音暴露 / Ndufs4

Outline of Final Research Achievements

Mild noise exposure causing temporary threshold shifts causes an irreversible decrease of inner hair cell synapses (cochlear synaptopathy) and is believed to cause early onset of age-related hearing loss and tinnitus. In this study, we assessed how glutamate toxicity, antioxidants, and mitochondrial dysfunction are involved in the development of noise-induced hearing loss, including cochlear synaptopathy. We established a model mouse of noise-induced cochlear synaptopathy in CBA/CaJ and C57BL/6 mouse strains, representative mouse strains in inner ear research. In experiments using mice with impaired mitochondrial function (Ndufs4 knockout mice), we found that Ndufs4 is broadly expressed in the cochlea, that deletion of Ndufs4 causes deterioration of low-frequency hearing after moderate noise exposure, and that deletion of Ndufs4 does not contribute to the development of cochlear synaptopathy.

Free Research Field

耳鼻咽喉・頭頸部外科学

Academic Significance and Societal Importance of the Research Achievements

一過性の聴力低下が生じる程度の騒音曝露により、有毛細胞が無傷であっても不可逆的な内有毛細胞シナプスの減少が生じ（cochlear synaptopathy）、加齢性難聴の早期発症や耳鳴症の原因となるとされる。本研究で確立した代表的なマウス系統のシナプス障害モデルは、今後のcochlear synaptopathy研究の基礎となる。またNdufs4の欠失によるミトコンドリア機能低下ではcochlear synaptopathyの発症が促進されないことが示され、cochlear synaptopathyの更なる病態解明の手掛かりになると考えられる。