Research on the inner ear cochlear cell protection system to elucidate the pathomechanism of sensorineural hearing loss

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06589
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47040:Pharmacology-related
• Research Institution: Setsunan University
• Principal Investigator: Yoneyama Masanori 摂南大学, 薬学部, 教授 (00411710)
• Co-Investigator(Kenkyū-buntansha): 山口 太郎 摂南大学, 薬学部, 講師 (30710701)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 感音性難聴 / 内耳 / らせん靱帯 / オートファジー / 外らせん溝細胞

Outline of Final Research Achievements

In the present study, we prepared an animal model of permanent hearing loss and sought to determine whether rapamycin (autophagy activator) have preventive effect on noise-induced hearing loss in the model mice. To determine the activation of autophagy following noise exposure, we evaluated the expression of LC3-II (LC3 = LC3-II/LC3-I, autophagy marker) in the cochlea after a 1-h exposure to noise at 110 dB SPL. Immunoblot analysis revealed that noise exposure produced a dramatic increase in the LC3-II level of the cochlea at 1-h post-exposure. Moreover, rapamycin significantly alleviated hearing impairment induced by exposure to noise at 110-dB SPL. In addition, immunohistochemistry analysis revealed that rapamycin was effective in enhancing expression of LC3 in the cochlear lateral wall. Taken together, our data suggest that autophagy activator is a candidate of preventive drugs for sensorineural hearing loss.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

聴覚組織において、蝸牛らせん靱帯には音響刺激に対してオートファジーによる細胞保護システムが存在し、その破綻に酸化ストレスが関わっていること、及び薬物処置により活性化させることで外部からの強大な音刺激による内耳障害を予防することが出来る可能性が示唆された。本研究結果は、聴覚機能障害の発症メカニズムを理解し、より適切な感音性難聴の治療を提供する上で極めて意義深いものであり、重要かつ社会的ニーズの高いものである。