Elucidation of the processing mechanism of reactive oxygen species in the inner ear in MnSOD genetically modified animals

• Project/Area Number: 15H06174
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Otorhinolaryngology
• Research Institution: The University of Tokyo
• Principal Investigator: Kinoshita Makoto 東京大学, 医学部附属病院, 登録診療員 (10755648)
• Project Period (FY): 2015-08-28 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: MnSOD / SOD2 / 騒音性難聴 / 酸化ストレス / ミトコンドリア / ＭｎＳＯＤ / ＳＯＤ２

Outline of Final Research Achievements

Manganese superoxide dismutase (MnSOD) is one of the antioxidant enzymes acting within the mitochondria. To investigate the pathological role of mitochondrial antioxidant stress in the cochlea, we generated systemic MnSOD heterozygous knockout (Sod2+/-) mice, and investigated hearing loss and histological damage after noise exposure.
The mean thresholds of auditory brainstem responses were significantly worse in the Sod2+/- group on post-noise days 7 and 14. Histologically, compared with control group, outer hair cell survival rate in the Sod2+/- group was significantly decreased in all cochlear turns.
We showed that delay of hearing recovery and outer hair cell damage occur after noise exposure with decreasing MnSOD. These findings suggest that MnSOD has important role to reduce reactive oxygen species in hair cell, thereby protecting from noise induced hearing loss.

Research Products

• [Journal Article] Manganese superoxide dismutase influences the extent of noise-induced hearing loss in mice. (2017)
  • Author(s): Tuerdi A, Kinoshita M, Kamogashira T, Fujimoto C, Iwasaki S, Shimizu T, Yamasoba T
  • Journal Title: Neurosci Lett Volume: 642 Pages: 123-128
  • DOI: 10.1016/j.neulet.2017.02.003
  • Peer Reviewed / Open Access
• [Presentation] 騒音暴露による内耳酸化ストレスがMnSODヘテロ欠損マウスの聴覚に及ぼす影響 (2016)
  • Author(s): Aynur Turdi、木下淳、藤本千里、岩崎真一、山岨達也
  • Organizer: 第16回日本抗加齢医学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2016-06-10
• [Presentation] Mn-SOD affects Noise Induced Hearing Loss (2016)
  • Author(s): Aynur Turdi, Makoto Kinoshita, Chisato Fujimoto, Shinichi Iwasaki, Tatsuya yamasoba
  • Organizer: Association for Research in Otolaryngology, 39th Annual Mid Winter Meeting
  • Place of Presentation: サンディエゴ（USA）
  • Year and Date: 2016-02-20
  • Int'l Joint Research
• [Presentation] Mn-SOD affects Noise Induced Hearing Loss (2015)
  • Author(s): Ａynur Turdi, Makoto Kinoshita, Chisato Fujimoto, Shinichi Iwasaki, Tatsuya yamasoba
  • Organizer: 13th Japan-Taiwan Conference on Otolaryngology-Head and Neck Surgery
  • Place of Presentation: 一ツ橋ホール（東京）
  • Year and Date: 2015-12-03
  • Int'l Joint Research