Establishment of quantitative methods to evaluate mitochondrial function in the inner ear

• Project/Area Number: 15K10743
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: The University of Tokyo
• Principal Investigator: Fujimoto Chisato 東京大学, 医学部附属病院, 登録診療員 (60581882)
• Research Collaborator: KINOSHITA MAKOTO ; KAMOGASHIRA TERU
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
• Keywords: 内耳 / ミトコンドリア / 加齢 / 有毛細胞 / 蝸牛 / 電子伝達系 / ミトコンドリア膜電位 / 酸化ストレス

Outline of Final Research Achievements

We established quantitative method to evaluate mitochondrial membrane potential by using JC-1 fluorescence dye in HEI-OC1 auditory cell line and cochlear explants. We also established quantitative method to evaluate mitochondrial respiratory function by using an extracellular flux analyzer in HEI-OC1 auditory cell line and cochlear explants.
We then evaluated mitochondrial function of a senescence model of HEI-OC1 cells induced by H2O2 exposure, by these established quantitative methods.
We revealed that relative value of oxygen consumption rate on FCCP injection was dose dependently decreased in the H2O2-exposed cells. This suggests damage of the mitochondrial respiratory capacity in the senescence model.We also revealed that JC-1 red/green ratio was decreased in a dose-dependent manner in the H2O2-exposed cells. This suggests decreased mitochondrial membrane potential in the senescence model.

Research Products

• [Journal Article] Japanese standard for clinical stabilometry assessment: Current status and future directions (2018)
  • Author(s): Yamamoto Masahiko、Ishikawa Kazuo、Aoki Mitsuhiro、Mizuta Keisuke、Ito Yatsuji、Asai Masatsugu、Shojaku Hideo、Yamanaka Toshiaki、Fujimoto Chisato、Murofushi Toshihisa、Yoshida Tomoe
  • Journal Title: Auris Nasus Larynx Volume: 45 Issue: 2 Pages: 201-206
  • DOI: 10.1016/j.anl.2017.06.006
  • Peer Reviewed
• [Journal Article] Clinical features of otolith organ-specific vestibular dysfunction (2018)
  • Author(s): Fujimoto C, Suzuki S, Kinoshita M, Egami N, Sugasawa K, Iwasaki S
  • Journal Title: Clinical Neurophysiology Volume: 129 Issue: 1 Pages: 238-245
  • DOI: 10.1016/j.clinph.2017.11.006
  • Peer Reviewed
• [Journal Article] Noisy vestibular stimulation increases gait speed in normals and in bilateral vestibulopathy (2018)
  • Author(s): Iwasaki Shinichi、Fujimoto Chisato、Egami Naoya、Kinoshita Makoto、Togo Fumiharu、Yamamoto Yoshiharu、Yamasoba Tatsuya
  • Journal Title: Brain Stimulation Volume: - Issue: 4 Pages: 709-715
  • DOI: 10.1016/j.brs.2018.03.005
  • Peer Reviewed
• [Journal Article] Effects of peripheral vestibular dysfunction on dynamic postural stability measured by the functional reach test and timed up and go test (2017)
  • Author(s): Nishi T, Kamogashira T, Fujimoto C, Kinoshita M, Egami N, Sugasawa K, Yamasoba T, Iwasaki S
  • Journal Title: Annals of Otology, Rhinology & Laryngology Volume: 126 Issue: 6 Pages: 438-444
  • DOI: 10.1177/0003489417700439
  • Peer Reviewed
• [Journal Article] Autophagy is essential for hearing in mice. (2017)
  • Author(s): Fujimoto C, Iwasaki S, Urata S, Morishita H, Sakamaki Y, Fujioka M, Kondo K, Mizushima N, Yamasoba T
  • Journal Title: Cell Death Dis Volume: 印刷中 Issue: 5 Pages: e2780-e2780
  • DOI: 10.1038/cddis.2017.194
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Functionally and morphologically damaged mitochondria observed in auditory cells under senescence-inducing stress. (2017)
  • Author(s): Kamogashira T, Hayashi K, Fujimoto C, Iwasaki S, Yamasoba T
  • Journal Title: NPJ Aging Mech Dis Volume: 3 Issue: 1 Pages: 2-2
  • DOI: 10.1038/s41514-017-0002-2
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Macrophage recruitment, but not interleukin 1 beta activation, enhances noise-induced hearing damage (2017)
  • Author(s): Mizushima Yu、Fujimoto Chisato、Kashio Akinori、Kondo Kenji、Yamasoba Tatsuya
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 493 Issue: 2 Pages: 894-900
  • DOI: 10.1016/j.bbrc.2017.09.124
  • Peer Reviewed
• [Journal Article] VEMP（vestibular evoked myogenic potential） (2017)
  • Author(s): 藤本千里
  • Journal Title: 耳鼻咽喉科・頭頸部外科 Volume: 89 Pages: 143-148
• [Journal Article] 頭痛に対する向精神薬の適応と使い方 (2017)
  • Author(s): 藤本千里
  • Journal Title: Monthly Book ENTONI Volume: 210 Pages: 86-89
• [Journal Article] Effect of Noisy Galvanic Vestibular Stimulation on Ocular Vestibular-Evoked Myogenic Potentials to Bone-Conducted Vibration (2017)
  • Author(s): Iwasaki S, Karino S, Kamogashira T, Togo F, Fujimoto C, Yamamoto Y, Yamasoba T
  • Journal Title: Front Neurol Volume: 8 Pages: 26-26
  • DOI: 10.3389/fneur.2017.00026
  • Peer Reviewed / Open Access
• [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
• [Journal Article] Noisy galvanic vestibular stimulation induces a sustained improvement in body balance in elderly adults (2016)
  • Author(s): Fujimoto C, Yamamoto Y, Kamogashira T, Kinoshita M, Egami N, Uemura Y, Togo F, Yamasoba T, Iwasaki S
  • Journal Title: Sci Rep Volume: 6 Issue: 1 Pages: 37575-37575
  • DOI: 10.1038/srep37575
  • Peer Reviewed / Open Access
• [Journal Article] Vestibular Evoked Myogenic Potentials in Vestibular Migraine: Do They Help Differentiating From Menière's Disease? (2016)
  • Author(s): Inoue A, Egami N, Fujimoto C, Kinoshita M, Yamasoba T, Iwasaki S
  • Journal Title: Ann Otol Rhinol Laryngol Volume: 125 Pages: 931-937
  • Peer Reviewed
• [Journal Article] Denervation of nasal mucosa induced by posterior nasal neurectomy suppresses nasal secretion, not hypersensitivity, in an allergic rhinitis rat model. (2016)
  • Author(s): Nishijima H, Kondo K, Toma-Hirano M, Iwasaki S, Kikuta S, Fujimoto C, Ueha R, Kagoya R, Yamasoba T
  • Journal Title: Lab Invest Volume: 96 Issue: 9 Pages: 981-993
  • DOI: 10.1038/labinvest.2016.72
  • Peer Reviewed
• [Journal Article] Association of the upregulated expression of focal adhesion kinase with poor prognosis and tumor dissemination in hypopharyngeal cancer. (2016)
  • Author(s): Omura G, Ando M, Saito Y, Kobayashi K, Yoshida M, Ebihara Y, Kanaya K, Fujimoto C, Sakamoto T, Kondo K, Asakage T, Yamasoba T
  • Journal Title: Head Neck. Volume: Published on line Issue: 8 Pages: 1164-1169
  • DOI: 10.1002/hed.24176
  • Peer Reviewed
• [Journal Article] Human Papillomavirus 16 Physical Status and the TP53 Codon 72 Polymorphism in Japanese HPV-Positive Oropharyngeal Cancer Patients. (2016)
  • Author(s): Saito Y, Ando M, Fujimoto C, Omura G, Kobayashi K, Asakage T, Yamasoba T.
  • Journal Title: ORL J Otorhinolaryngol Relat Spec. Volume: 78(1) Issue: 1 Pages: 46-54
  • DOI: 10.1159/000442354
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Characteristics of vertigo and the affected vestibular nerve systems in idiopathic bilateral vestibulopathy. (2016)
  • Author(s): Fujimoto C, Kinoshita M, Kamogashira T, Egami N, Sugasawa K, Yamasoba T, Iwasaki S.
  • Journal Title: Acta Otolaryngol. Volume: 136(1) Issue: 1 Pages: 43-47
  • DOI: 10.3109/00016489.2015.1082193
  • Peer Reviewed
• [Journal Article] 重心動揺検査の現状と将来展望 ラバー負荷検査の有用性と今後の展望 (2016)
  • Author(s): 藤本千里
  • Journal Title: Equilibrium Res Volume: 75 Pages: 142-146
  • Peer Reviewed
• [Journal Article] 【めまい-新しい流れとその周辺-】 新しい検査・解釈 重心動揺計 (2016)
  • Author(s): 藤本千里
  • Journal Title: JOHNS Volume: 32 Pages: 33-35
• [Journal Article] ラバー負荷検査の有用性と今後の展望 (2016)
  • Author(s): 藤本千里
  • Journal Title: Equilibrium Res Volume: in press
  • NAID: 130005254879
  • Peer Reviewed
• [Journal Article] Prognostic value of p16 expression irrespective of human papillomavirus status in patients with oropharyngeal carcinoma. (2015)
  • Author(s): Saito Y, Yoshida M, Omura G, Kobayashi K, Fujimoto C, Ando M, Sakamoto T, Asakage T, Yamasoba T.
  • Journal Title: Jpn J Clin Oncol. Volume: 45(9) Issue: 9 Pages: 828-836
  • DOI: 10.1093/jjco/hyv085
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Reactive Oxygen Species, Apoptosis, and Mitochondrial Dysfunction in Hearing Loss. (2015)
  • Author(s): Kamogashira T, Fujimoto C, Yamasoba T
  • Journal Title: Biomed Research International Volume: 2015 Pages: 617207-617207
  • DOI: 10.1155/2015/617207
  • Peer Reviewed / Open Access
• [Journal Article] Maxillary carcinosarcoma: Identification of a novel MET mutation in both carcinomatous and sarcomatous components through next generation sequencing (2015)
  • Author(s): Mizuo Ando, Yuki Saito, Teppei Morikawa, Go Omura, Kenya Kobayashi, Ken Akashi, Masafumi Yoshida, Yasuhiro Ebihara, Chisato Fujimoto, Masashi Fukayama, Tatsuya Yamasoba, Takahiro Asakage
  • Journal Title: Head and Neck Volume: 未定 Issue: 12
  • DOI: 10.1002/hed.24043
  • Peer Reviewed
• [Journal Article] Clinical characteristics of patients with abnormal ocular/cervical vestibular evoked myogenic potentials in the presence of normal caloric responses. (2015)
  • Author(s): Iwasaki S, Fujimoto C, Kinoshita M, Kamogashira T, Egami N, Yamasoba T.
  • Journal Title: Ann Otol Rhinol Laryngol. Volume: 124(6) Issue: 6 Pages: 458-465
  • DOI: 10.1177/0003489414564997
  • Peer Reviewed
• [Presentation] Noisy galvanic vestibular stimulation induces a sustained improvement in body balance in patients with bilateral vestibulopathy (2018)
  • Author(s): Chisato Fujimoto, Shinichi Iwasaki, Naoya Egami, Yoshiharu Yamamoto, Tatsuya Yamasoba
  • Organizer: ARO 41st Annual MidWinter Meeting
  • Int'l Joint Research
• [Presentation] 有毛細胞における恒常的オートファジーは聴覚機能に重要である (2017)
  • Author(s): 藤本千里、岩崎真一、浦田真次、藤岡正人、近藤健二、山岨達也
  • Organizer: 第118回日本耳鼻咽喉科学会
• [Presentation] オートファジー活性の低下による有毛細胞の変性 (2017)
  • Author(s): 藤本千里、岩崎真一、浦田真次、藤岡正人、近藤健二、山岨達也
  • Organizer: 第17回日本抗加齢医学会
• [Presentation] Autophagy is essential for hearing in mice  (2017)
  • Author(s): Chisato Fujimoto
  • Organizer: IFOS 2017
  • Int'l Joint Research
• [Presentation] 経皮的ノイズ前庭電気刺激の長期刺激が両側前庭障害患者の体平衡機能に及ぼす影響 (2017)
  • Author(s): 藤本千里、岩崎真一、江上直也、木下淳、川原拓也、上村夕香理、菅澤恵子、山岨達也
  • Organizer: 第76回日本めまい平衡医学会
• [Presentation] 経皮的ノイズ前庭電気刺激による体平衡機能改善効果 (2017)
  • Author(s): 藤本千里、岩崎真一、鴨頭輝、木下淳、江上直也、山岨達也
  • Organizer: 第15回姿勢と歩行研究会
  • Place of Presentation: 興和株式会社東京支店(東京都・中央区)
• [Presentation] Video head impulse testにおけるcatch-up saccadeの性状と温度刺激検査におけるcanal paresisとの関連 (2016)
  • Author(s): 藤本千里、岩崎真一、鴨頭輝、木下淳、鈴木さやか、江上直也、牛尾宗貴、菅澤恵子、山岨達也
  • Organizer: 第75回日本めまい平衡医学会総会・学術講演会
  • Place of Presentation: 大阪国際会議場（大阪府・大阪市）
  • Year and Date: 2016-10-27
• [Presentation] 温度刺激検査で一側半規管麻痺を呈した症例におけるvideo head impulse testのcatch-up saccadeについて (2016)
  • Author(s): 藤本千里、岩崎真一、鴨頭輝、木下淳、鈴木さやか、江上直也、牛尾宗貴、山岨達也
  • Organizer: 第26回日本耳科学会・学術講演会
  • Place of Presentation: ホテル国際21(長野県・長野市)
  • Year and Date: 2016-10-05
• [Presentation] 経皮的ノイズ前庭電気刺激が健常者の立位体平衡機能に及ぼす影響 (2016)
  • Author(s): 藤本千里、岩崎真一、鴨頭輝、木下淳、江上直也、山岨達也
  • Organizer: 第16回日本抗加齢医学会総会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2016-06-10
• [Presentation] Effect of noisy galvanic vestibular stimulation on gait performance in patients with bilateral vestibulopathy. (2016)
  • Author(s): Chisato Fujimoto, Shinichi Iwasaki, Teru Kamogashira, Makoto Kinoshita, Naoya Egami, Yukari Uemura, Fumiharu Togo, Yoshiharu Yamamoto and Tatsuya Yamasoba
  • Organizer: 29th Barany Society Meeting
  • Place of Presentation: Seoul (Korea)
  • Year and Date: 2016-06-05
  • Int'l Joint Research
• [Presentation] 経皮的ノイズ前庭電気刺激による長期的な静的体平衡機能改善効果 (2016)
  • Author(s): 藤本千里、岩崎真一、鴨頭輝、木下淳、江上直也、山岨達也
  • Organizer: 第117回日本耳鼻咽喉科学会・学術講演会
  • Place of Presentation: 名古屋国際会議場（愛知県・名古屋市）
  • Year and Date: 2016-05-18
• [Presentation] Noisy galvanic vestibular stimulation provides sustained improvement of body balance (2016)
  • Author(s): Chisato Fujimoto, Shinichi Iwasaki, Teru Kamogashira, Makoto Kinoshita Naoya Egami, Yukari Uemura, Fumiharu Togo, Yoshiharu Yamamoto and Tatsuya Yamasoba
  • Organizer: ARO 39th MidWinter Meeting
  • Place of Presentation: San Diego (USA)
  • Year and Date: 2016-02-20
  • Int'l Joint Research
• [Presentation] 重心動揺検査の現状と将来展望 「ラバー負荷検査の有用性と今後の展望」 (2015)
  • Author(s): 藤本千里
  • Organizer: 第74回日本めまい平衡医学会・学術講演会
  • Place of Presentation: 長良川国際会議場（岐阜県・岐阜市）
  • Year and Date: 2015-11-25
• [Presentation] 内耳有毛細胞におけるオートファジーの役割 (2015)
  • Author(s): 藤本千里
  • Organizer: 第9回オートファジー研究会・第3回「オートファジー」班会議
  • Place of Presentation: 淡路夢舞台国際会議場（兵庫県・淡路市）
  • Year and Date: 2015-11-15
• [Presentation] 温度刺激検査とラバー負荷重心動揺検査を複数回施行した前庭神経炎症例の検討 (2015)
  • Author(s): 藤本千里、岩崎真一、鴨頭輝、木下淳、鈴木さやか、江上直也、牛尾宗貴、山岨達也
  • Organizer: 第25回日本耳科学会・学術講演会
  • Place of Presentation: 長崎ブリックホール（長崎県・長崎市）
  • Year and Date: 2015-10-07
• [Remarks] オートファジーはマウスの聴覚に重要である
  • URL: http://www.h.u-tokyo.ac.jp/press/press_archives/20170511.html
• [Patent(Industrial Property Rights)] 前庭機能評価装置及び非ヒト動物における前庭機能の評価方法 (2015)
  • Inventor(s): 岩崎真一、松本有、藤本千里、鴨頭輝
  • Industrial Property Rights Holder: 岩崎真一、松本有、藤本千里、鴨頭輝
  • Industrial Property Rights Type: 特許
  • Filing Date: 2015
  • Acquisition Date: 2018