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Investigation of the role of necroptosis in the inner ear diseases and its application for treatments

Research Project

Project/Area Number 18K09370
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56050:Otorhinolaryngology-related
Research InstitutionNagoya City University (2019-2021)
The University of Tokyo (2018)

Principal Investigator

Iwasaki Shinichi  名古屋市立大学, 医薬学総合研究院(医学), 教授 (10359606)

Co-Investigator(Kenkyū-buntansha) 吉川 弥生  東京大学, 医学部附属病院, 届出研究員 (00452350)
樫尾 明憲  東京大学, 医学部附属病院, 准教授 (20451809)
藤本 千里  東京大学, 医学部附属病院, 講師 (60581882)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords内耳障害 / アポトーシス / ネクローシス / ネクロプトーシス / アミノ配糖体 / 有毛細胞 / 蝸牛 / 内耳 / 難聴
Outline of Final Research Achievements

Historically, two forms of cell death have been recognized: necrosis as ‘accidental’ and apoptosis as ‘programmed’. Recently, genetically programmed form of necrosis termed ‘necroptosis’ has been reported. We investigated the involvement of necroptosis and apoptosis in gentamicin (GM) ototoxicity to identify potential therapeutic targets. We examined organotypic cultures of P3 ICR mice cochlear explants. We showedd necrotic and apoptotic cells proportion and the levels of typical antibody in hair cells decreased after treating with different concentration of ZVAD (caspase inhibitor) or Nec-1(necrosis inhibitor).
Our findings suggest that GM-induced ototoxicity is caused by combination of necrosis, necroptosis, and apoptosis.

Academic Significance and Societal Importance of the Research Achievements

感音性難聴や末梢前庭障害等の内耳疾患は頻度の高い身体障害であるにもかかわらず、その根本的な治療は未だ確立されていない。薬剤性内耳障害や騒音性難聴、老人性難聴においては、それらの発症に有毛細胞内の酸化ストレスに起因するアポトーシスが深く関与することが示されている。しかしながら、これらの障害に対する抗酸化剤やアポトーシス阻害薬の効果は部分的であり、非アポトーシス細胞死の関与が予想される。
本研究では、耳毒性薬物による内耳障害には、アポトーシスのみならず、ネクローシスやネクロプトーシスも関与することを明らかにした。この研究成果は、内耳障害に対する新規治療の開発に貢献するものである。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (28 results)

All 2021 2020 2019 2018

All Journal Article (16 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 16 results,  Open Access: 11 results) Presentation (12 results) (of which Int'l Joint Research: 4 results,  Invited: 8 results)

  • [Journal Article] Diagnostic and therapeutic strategies of the Japan Society of Equilibrium Research.2021

    • Author(s)
      Iwasaki S, Shojaku, H, Murofushi T, Seo T, Kitahara T, Origasa H, Watanabe Y, Suzuki M, Takeda N on behalf of Committee for Clinical Practice Guidelines of Japan Society of Equilibrium Research.
    • Journal Title

      Auris Nasus Larynx

      Volume: 48 Issue: 3 Pages: 15-22

    • DOI

      10.1016/j.anl.2021.08.008

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cervical Vestibular Evoked Myogenic Potentials That Are Absent at 500 Hz But Present at 1000 Hz Are Characteristic of Endolymphatic Hydrops-Related Disease2021

    • Author(s)
      Fujimoto Chisato、Kinoshita Makoto、Ichijo Kentaro、Oka Mineko、Kamogashira Teru、Sugasawa Keiko、Kawahara Takuya、Yamasoba Tatsuya、Iwasaki Shinichi
    • Journal Title

      Ear & Hearing

      Volume: Publish Ahead of Print Issue: 5 Pages: 1306-1312

    • DOI

      10.1097/aud.0000000000001017

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Minimally important differences for subjective improvement in postural stability in patients with bilateral vestibulopathy2021

    • Author(s)
      Fujimoto Chisato、Kawahara Takuya、Kinoshita Makoto、Ichijo Kentaro、Oka Mineko、Kamogashira Teru、Sugasawa Keiko、Yamasoba Tatsuya、Iwasaki Shinichi
    • Journal Title

      Neuroscience Letters

      Volume: 747 Pages: 135706-135706

    • DOI

      10.1016/j.neulet.2021.135706

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Imaging manifestations on sequential magnetic resonance imaging in pharyngolaryngeal involvement by varicella zoster virus.2021

    • Author(s)
      Inagaki A, Kojima A, Ogawa M, Sakata T, Iwasaki S.
    • Journal Title

      J Neurovirol.

      Volume: 27 Issue: 1 Pages: 186-190

    • DOI

      10.1007/s13365-021-00953-5

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Classification of the Chorda Tympani2020

    • Author(s)
      Uranaka Tsukasa、Matsumoto Yu、Hoshi Yujiro、Iwasaki Shinichi、Kakigi Akinobu、Yamasoba Tatsuya
    • Journal Title

      Otology & Neurotology

      Volume: Publish Ahead of Print Issue: 3 Pages: e355-e362

    • DOI

      10.1097/mao.0000000000002998

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Prediction of Vestibular Dysfunction by Applying Machine Learning Algorithms to Postural Instability2020

    • Author(s)
      Kamogashira Teru、Fujimoto Chisato、Kinoshita Makoto、Kikkawa Yayoi、Yamasoba Tatsuya、Iwasaki Shinichi
    • Journal Title

      Frontiers in Neurology

      Volume: 11 Pages: 1-1

    • DOI

      10.3389/fneur.2020.00007

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Utriculo-ocular pathway dysfunction is more frequent in vestibular migraine than probable vestibular migraine.2020

    • Author(s)
      Fujimoto C, Kamogashira T, Takenouchi S, Kinoshita M, Sugasawa K, Kawahara T, Yamasoba T, Iwasaki S
    • Journal Title

      J Neurol

      Volume: 267 Issue: 8 Pages: 2340-2346

    • DOI

      10.1007/s00415-020-09851-y

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Acute bilateral vestibulopathy with simultaneous involvement of both superior and inferior vestibular nerves2019

    • Author(s)
      Ichijo Kentaro、Kinoshita Makoto、Fujimoto Chisato、Uranaka Tsukasa、Kikkawa Yayoi S.、Sugasawa Keiko、Yamasoba Tatsuya、Iwasaki Shinichi
    • Journal Title

      Auris Nasus Larynx

      Volume: 19 Issue: 5 Pages: 30324-4

    • DOI

      10.1016/j.anl.2019.07.007

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Noisy galvanic vestibular stimulation has a greater ameliorating effect on posture in unstable subjects: a feasibility study2019

    • Author(s)
      Fujimoto Chisato、Kinoshita Makoto、Kamogashira Teru、Egami Naoya、Kawahara Takuya、Uemura Yukari、Yamamoto Yoshiharu、Yamasoba Tatsuya、Iwasaki Shinichi
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 7-7

    • DOI

      10.1038/s41598-019-53834-7

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Alteration of Musashi1 Intra-cellular Distribution During Regeneration Following Gentamicin-Induced Hair Cell Loss in the Guinea Pig Crista Ampullaris2019

    • Author(s)
      Kinoshita Makoto、Fujimoto Chisato、Iwasaki Shinichi、Kashio Akinori、Kikkawa Yayoi S.、Kondo Kenji、Okano Hideyuki、Yamasoba Tatsuya
    • Journal Title

      Frontiers in Cellular Neuroscience

      Volume: 13 Pages: 481-481

    • DOI

      10.3389/fncel.2019.00481

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Progression of Peripheral Vestibular Dysfunctions in Patients With a Mitochondrial A3243G Mutation2019

    • Author(s)
      Inoue Aki、Iwasaki Shinichi、Fujimoto Chisato、Kinoshita Makoto、Yamasoba Tatsuya
    • Journal Title

      Otology & Neurotology

      Volume: 40 Issue: 3 Pages: 359-364

    • DOI

      10.1097/mao.0000000000002091

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Aging Is a Risk Factor for Utricular Dysfunction in Idiopathic Benign Paroxysmal Positional Vertigo2018

    • Author(s)
      Fujimoto Chisato、Kawahara Takuya、Kinoshita Makoto、Kikkawa Yayoi S.、Sugasawa Keiko、Yagi Masato、Yamasoba Tatsuya、Iwasaki Shinichi、Murofushi Toshihisa
    • Journal Title

      Frontiers in Neurology

      Volume: 9 Pages: 1049-1049

    • DOI

      10.3389/fneur.2018.01049

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Noisy Galvanic Vestibular Stimulation Sustainably Improves Posture in Bilateral Vestibulopathy2018

    • Author(s)
      Fujimoto Chisato、Egami Naoya、Kawahara Takuya、Uemura Yukari、Yamamoto Yoshiharu、Yamasoba Tatsuya、Iwasaki Shinichi
    • Journal Title

      Frontiers in Neurology

      Volume: 9 Pages: 900-900

    • DOI

      10.3389/fneur.2018.00900

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The adhesion molecule cadherin 11 is essential for acquisition of normal hearing ability through middle ear development in the mouse2018

    • Author(s)
      Kiyama Yuji、Kikkawa Yayoi S.、Kinoshita Makoto、Matsumoto Yu、Kondo Kenji、Fujimoto Chisato、Iwasaki Shinichi、Yamasoba Tatsuya、Manabe Toshiya
    • Journal Title

      Laboratory Investigation

      Volume: 98 Issue: 11 Pages: 1364-1374

    • DOI

      10.1038/s41374-018-0083-y

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Noisy vestibular stimulation increases gait speed in normals and in bilateral vestibulopathy2018

    • 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

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical features of otolith organ-specific vestibular dysfunction2018

    • 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

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] 高齢者のめまい:診断と対策2021

    • Author(s)
      岩﨑真一
    • Organizer
      令和3年度 日本医師会生涯教育講座
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 目で見る眼球運動異常と病態生理:先天性眼振について2021

    • Author(s)
      岩﨑真一
    • Organizer
      第80回日本めまい平衡医学会総会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 両側前庭障害の診断と対策2020

    • Author(s)
      岩﨑真一
    • Organizer
      日耳鼻埼玉県地方部会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] Bilateral vestibulopathy: How to treat and manage? Overview and epidemiology of bilateral vestibulopathy in Japan.2020

    • Author(s)
      Shinichi Iwasaki
    • Organizer
      第79回日本めまい平衡医学会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] Noisy galvanic vestibular stimulation as a treatment for bilateral vestibulopathy.2019

    • Author(s)
      Shinichi Iwasaki
    • Organizer
      3rd Seoul National University Bundang Hospital Dizziness Center Symposium
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Ameliorating effect of noisy galvanic vestibular stimulation on postural stability is greater in originally more unstable subjects.2019

    • Author(s)
      Shinichi Iwasaki, Chisato Fujimoto, Takuya Kawahara, Yukari Uemura, Tatsuya Yamasoba
    • Organizer
      CORLAS Meeting 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Differential Morphology to Hair Cells by Gentamicin in Rat Cochlear Organotypic Cultures2019

    • Author(s)
      Gao Ying, Makoto Kinoshita, Shinichi Iwasaki, Akinori Kashio, Yayoi Kikkawa, Tatsuya Yamasoba
    • Organizer
      第29回日本耳科学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 60周年記念シンポジウム「前庭刺激検査の過去と未来」Video head impulse testの原理と実際2018

    • Author(s)
      岩﨑真一
    • Organizer
      第77回日本めまい平衡医学会総会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Video head impulse test (vHIT)のコツとピットフォール2018

    • Author(s)
      岩﨑真一
    • Organizer
      第28回日本耳科学会総会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Frequency characteristics of somatoform vertigo and dizziness, bilateral vestibulopathy, and spinocerebellar degeneration.2018

    • Author(s)
      Iwasaki S, Kinoshita M, Fujimoto C, Egami N, Yamasoba T.
    • Organizer
      2018 Annual CORLAS Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Effects of long-term noisy vestibular stimulation on body balance in bilateral vestibulopathy.2018

    • Author(s)
      Iwasaki S, Fujimoto C, Egami N, Kawahara T, Uemura Y, Yamamoto Y, Yamasoba T.
    • Organizer
      XXX Barany Society Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] シンポジウムAMED研究:ノイズ前庭電気刺激による前庭障害患者の体平衡機能改善機器の開発2018

    • Author(s)
      岩﨑真一
    • Organizer
      第119回 日本耳鼻咽喉科学会総会
    • Related Report
      2018 Research-status Report
    • Invited

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Published: 2018-04-23   Modified: 2023-01-30  

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