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Sensorineural olfactory disorder: molecular analyses of pathophysiology and development of therapeutic strategy

Research Project

Project/Area Number 26293366
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Otorhinolaryngology
Research InstitutionThe University of Tokyo

Principal Investigator

Kondo Kenji  東京大学, 医学部附属病院, 准教授 (40334370)

Co-Investigator(Kenkyū-buntansha) 菊田 周  東京大学, 医学部附属病院, 助教 (00555865)
有田 誠  国立研究開発法人理化学研究所, 統合生命医科学研究センター, チームリーダー (80292952)
野村 務  埼玉医科大学, 医学部, 講師 (20228365)
Research Collaborator YAMASOBA TATSUYA  東京大学, 医学部附属病院, 教授 (60251302)
BABA MIYUKI  東京逓信病院, 耳鼻咽喉科, 医長
UEHA RUMI  東京大学, 医学部附属病院, 助教 (10597131)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥16,380,000 (Direct Cost: ¥12,600,000、Indirect Cost: ¥3,780,000)
Fiscal Year 2016: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2015: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2014: ¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000)
Keywords嗅神経傷害 / 加齢変化 / 再生 / 脂質メディエーター / 嗅覚 / 脂肪酸 / 慢性副鼻腔炎 / CFD / 鼻科学 / 嗅覚医学 / 嗅神経障害 / 神経再生
Outline of Final Research Achievements

(1) Caloric restriction exacerbated regeneration of the olfactory neuroepithelium after injury by methimazole. Downregulation of proliferative activity of basal cells in neuroepithelium by caloric restriction appeared to play important role in these findings. (2) During the regeneration of the olfactory neuroepithelium, lipid mediators generated through metabolism by 12/15 lipoxygenase (12/15 LOX) was increased. 12/15 LOX-positive cells were transiently infiltrated into the regenerating olfactory mucosa, suggesting that the composition of tissue fatty acid is associated with the regenerative process of the olfactory neuroepithelium. (3) Intranasal administration of cigarette smoke solution (CSS) suppressed the recovery of neuroepithelium after injury. CSS administration decreased the ORN injury-induced IGF-1 expression. Administration of recombinant human IGF-1 prevented the CSS-induced suppression of neuroepithelial recovery.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report

Research Products

(38 results)

All 2017 2016 2015 2014 Other

All Journal Article (11 results) (of which Peer Reviewed: 9 results,  Open Access: 6 results,  Acknowledgement Compliant: 7 results) Presentation (24 results) (of which Int'l Joint Research: 4 results,  Invited: 3 results) Remarks (3 results)

  • [Journal Article] Ethmoidectomy combined with superior meatus enlargement increases olfactory airflow2017

    • Author(s)
      Nishijima H, Kondo K, Nomura T, Yamasoba T
    • Journal Title

      Laryngoscope Investigative Otolaryngology

      Volume: 印刷中 Pages: 136-146

    • DOI

      10.1002/lio2.59

    • Related Report
      2016 Annual Research Report
    • Open Access / Acknowledgement Compliant
  • [Journal Article] Longer latency of sensory response to intravenous odor injection predicts olfactory neural disorder.2016

    • Author(s)
      Kikuta S, Matsumoto Y, Kuboki A, Nakayama T, Asaka D, Otori N, Kojima H, Sakamoto T, Akinori K, Kanaya K, Ueha R, Kagoya R, Nishijima H, Toma-Hirano M, Kikkawa Y, Kondo K, Tsunoda K, Miyaji T, Yamaguchi T, Kataoka K, Mori K, Yamasoba T.
    • Journal Title

      Sci Rep.

      Volume: 6 Pages: 35361-35361

    • DOI

      10.1038/srep35361

    • NAID

      130006708720

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Cigarette Smoke Delays Regeneration of the Olfactory Epithelium in Mice.2016

    • Author(s)
      Ueha R, Ueha S, Sakamoto T, Kanaya K, Suzukawa K, Nishijima H, Kikuta S, Kondo K, Matsushima K, Yamasoba T.
    • Journal Title

      Neurotoxicity Research

      Volume: 30 Pages: 213-224

    • DOI

      10.1007/s12640-016-9617-5

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Damage to Olfactory Progenitor Cells Is Involved in Cigarette Smoke-Induced Olfactory Dysfunction in Mice.2016

    • Author(s)
      Ueha R, Ueha S, Kondo K, Sakamoto T, Kikuta S, Kanaya K, Nishijima H, Matsushima K, Yamasoba T.
    • Journal Title

      Am J Pathol

      Volume: 186 Pages: 579-586

    • DOI

      10.1016/j.ajpath.2015.11.009

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Novel scoring system and algorithm for classifying chronic rhinosinusitis: The JESREC Study.2015

    • Author(s)
      Tokunaga T, Sakashita M, Haruna T, Asaka D, Takeno S, Ikeda H, Nakayama T, Seki N, Ito S, Murata J, Sakuma Y, Yoshida N, Terada T, Morikura I, Sakaida H, Kondo K, Yamada K, Okano M, Ohtori N, Yoshikawa M, et al
    • Journal Title

      Allergy.

      Volume: Epub ahead of print Pages: 995-1003

    • DOI

      10.1111/all.12644

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Sensory deprivation disrupts homeostatic regeneration of newly generated olfactory sensory neurons after injury in adult mice.2015

    • Author(s)
      Kikuta S, Sakamoto T, Nagayama S, Kanaya K, Kinoshita M, Kondo K, Tsunoda K, Mori K, Yamasoba T.
    • Journal Title

      Journal of Neuroscience

      Volume: 35 Pages: 2484-14

    • DOI

      10.1523/jneurosci.2484-14.2015

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Effects of nasal septum perforation repair surgery on three-dimensional airflow: an evaluation using computational fluid dynamics2015

    • Author(s)
      Nomura T, Ushio M, Kondo K, Yamasoba T
    • Journal Title

      Eur Arch Otorhinolaryngol

      Volume: 272 Pages: 3327-3333

    • DOI

      10.1007/s00405-014-3438-z

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Correlation of basophil infiltration in nasal polyps with the severity of chronic rhinosinusitis2015

    • Author(s)
      Kagoya R, Kondo K, Baba S, Toma-Hirano M, Nishijima H, Suzukawa K, Kikuta S, Yamasoba T
    • Journal Title

      Ann Allergy Asthma Immunol

      Volume: 114 Pages: 30-35

    • DOI

      10.1016/j.anai.2014.09.017

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Treatment of neurological disorders by introducing mRNA in vivo using polyplex nanomicelles2015

    • Author(s)
      Baba M, Itaka K, Kondo K, Yamasoba T, Kataoka K.
    • Journal Title

      J Control Release.

      Volume: 201 Pages: 41-48

    • DOI

      10.1016/j.jconrel.2015.01.017

    • NAID

      120006348466

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Viral disruption of olfactory progenitors is exacerbated in allergic mice.2014

    • Author(s)
      Ueha R, Mukherjee S, Ueha S, de Almeida Nagata DE, Sakamoto T, Kondo K, Yamasoba T, Lukacs NW, Kunkel SL.
    • Journal Title

      Int Immunopharmacol

      Volume: 22 Pages: 242-247

    • DOI

      10.1016/j.intimp.2014.06.034

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Innate immune responses and neuroepithelial degeneration and regeneration in the mouse olfactory mucosa induced by intranasal administration of Poly(I:C).2014

    • Author(s)
      Kanaya K, Kondo K, Suzukawa K, Sakamoto T, Kikuta S, Okada K, Yamasoba T.
    • Journal Title

      Cell Tissue Res.

      Volume: 357 Pages: 279-99

    • DOI

      10.1007/s00441-014-1848-2

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Computational Fluid Dynamics analysis of olfactory airflow after ESS2016

    • Author(s)
      Hironobu Nishijima, Kenji Kondo, Tsutomu Nomura, and Tatsuya Yamasoba
    • Organizer
      Advances in Allergy and Rhinology Management, in conjunction with Rhinology Research Forum in Asia (RReFA) Annual Meeting
    • Place of Presentation
      Singapore, Singapore
    • Year and Date
      2016-12-02
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] マウス嗅上皮再生過程にタバコ煙が及ぼす影響とIGF-1の関与2016

    • Author(s)
      上羽瑠美,近藤健二,坂本幸士,鈴川圭吾,菊田 周,金谷佳織,西嶌大宣,山岨達也
    • Organizer
      第55回日本鼻科学会総会・学術講演会
    • Place of Presentation
      栃木県総合文化センター(栃木県宇都宮市)
    • Year and Date
      2016-10-13
    • Related Report
      2016 Annual Research Report
  • [Presentation] 嗅神経上皮傷害・再生過程における脂肪酸の関与2016

    • Author(s)
      近藤健二,金谷佳織,菊田 周,西嶌大宣,岩村 均,山岨達也,有田 誠,磯部洋輔
    • Organizer
      第55回日本鼻科学会総会・学術講演会
    • Place of Presentation
      栃木県総合文化センター(栃木県宇都宮市)
    • Year and Date
      2016-10-13
    • Related Report
      2016 Annual Research Report
  • [Presentation] Eosinophilic Cationic Proteinによる嗅細胞障害に対するインスリン点鼻投与の予防効果2016

    • Author(s)
      菊田 周,久保木章仁,坂本幸士,金谷香織,上羽瑠美,西嶌大宣,近藤健二,山岨達也
    • Organizer
      第55回日本鼻科学会総会・学術講演会
    • Place of Presentation
      栃木県総合文化センター(栃木県宇都宮市)
    • Year and Date
      2016-10-13
    • Related Report
      2016 Annual Research Report
  • [Presentation] 嗅上皮傷害後の組織再生におけるマクロファージの役割2016

    • Author(s)
      金谷佳織,近藤健二,坂本幸士,菊田 周,山岨達也
    • Organizer
      第55回日本鼻科学会総会・学術講演会
    • Place of Presentation
      栃木県総合文化センター(栃木県宇都宮市)
    • Year and Date
      2016-10-13
    • Related Report
      2016 Annual Research Report
  • [Presentation] 上鼻道の開放は嗅裂気流を増加させる-Computational Fluid Dynamicsを用いた検討-2016

    • Author(s)
      西嶌大宜,近藤健二,野村務,菊田周,上羽瑠美,山岨達也
    • Organizer
      第55回日本鼻科学会総会・学術講演会
    • Place of Presentation
      栃木県総合文化センター(栃木県宇都宮市)
    • Year and Date
      2016-10-13
    • Related Report
      2016 Annual Research Report
  • [Presentation] 加齢がマウス嗅上皮環境に及ぼす影響の解析-嗅覚前駆細胞,成長因子とサイトカイン-2016

    • Author(s)
      上羽瑠美,近藤健二.藤巻葉子,後藤多嘉緒,二藤隆春,山岨達也
    • Organizer
      第16回日本抗加齢医学会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-06-09
    • Related Report
      2016 Annual Research Report
  • [Presentation] カロリー制限が可逆的嗅上皮障害後の嗅神経細胞再生に与える影響と遺伝子について2016

    • Author(s)
      岩村均、近藤健二、山岨達也
    • Organizer
      第16回日本抗加齢医学会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-06-09
    • Related Report
      2016 Annual Research Report
  • [Presentation] Caloric restriction in mice reduces basal cell proliferation and neuroepithelial regeneration following olfactotoxic mucosal damage2016

    • Author(s)
      Iwamura H, Kondo K, Yamasoba T
    • Organizer
      17th International Symposium on Olfaction and Taste, ISOT
    • Place of Presentation
      Yokohama, Japan
    • Year and Date
      2016-06-05
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Olfactory airflow after endoscopic sinus surgery: an analysis using virtual surgery and computational fluid dynamics2016

    • Author(s)
      Nishijima H, Kondo K, Nomura T, Yamasoba T
    • Organizer
      17th International Symposium on Olfaction and Taste, ISOT
    • Place of Presentation
      Yokohama, Japan
    • Year and Date
      2016-06-05
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] タバコ煙が嗅上皮障害後再生に及ぼす影響に関する検証2016

    • Author(s)
      上羽瑠美,近藤健二,坂本幸士,菊田 周,藤巻葉子,金谷佳織,西嶌大宣,山岨達也
    • Organizer
      第117回 日本耳鼻咽喉科学会総会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2016-05-19
    • Related Report
      2016 Annual Research Report
  • [Presentation] インスリン点鼻投与による嗅細胞の細胞死抑制効果2016

    • Author(s)
      菊田 周,久保木章仁,松本 有,坂本幸士,金谷香織,和田 翠,籠谷領二,西嶌大宣,平野真希子,吉川弥生,近藤健二,山岨達也
    • Organizer
      第117回 日本耳鼻咽喉科学会総会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2016-05-19
    • Related Report
      2016 Annual Research Report
  • [Presentation] 上鼻道の開放は嗅裂気流を増加させる -Computational Fluid Dynamicsを用いた検討-2016

    • Author(s)
      西嶌大宣,近藤健二,野村務,山岨達也
    • Organizer
      第117回 日本耳鼻咽喉科学会総会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2016-05-19
    • Related Report
      2016 Annual Research Report
  • [Presentation] Cell dynamics in the olfactory neuroepithelium after injury: The effects of sensory deprivation and caloric restriction2015

    • Author(s)
      Kondo K
    • Organizer
      The 11th Research symposium on human natural defense system in conjunction with Rhinology research forum in Asia (RReFA) annual meeting 2015
    • Place of Presentation
      Yonsei University, Seoul, Korea
    • Year and Date
      2015-10-18
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] マウス嗅粘膜のカロリー制限による遺伝子発現の変化の網羅的解析2015

    • Author(s)
      岩村均、近藤健二、平野真希子、安藤瑞生、西嶌大宣、菊田周、鈴川佳吾、金谷佳織、安原一夫、山岨達也
    • Organizer
      第54回日本鼻科学会
    • Place of Presentation
      広島国際会議場(広島県・広島市)
    • Year and Date
      2015-10-02
    • Related Report
      2015 Annual Research Report
  • [Presentation] タバコ煙によるマウス嗅上皮障害に加齢変化が及ぼす影響の解析2015

    • Author(s)
      上羽瑠美、近藤健二、菊田周、坂本幸士、金谷佳織、西嶌大宣、山岨達也
    • Organizer
      第54回日本鼻科学会
    • Place of Presentation
      広島国際会議場(広島県・広島市)
    • Year and Date
      2015-10-02
    • Related Report
      2015 Annual Research Report
  • [Presentation] カロリー制限が可逆的嗅上皮障害後の嗅神経細胞再生に与える影響について2015

    • Author(s)
      岩村均、 近藤健二、 菊田周、 鈴川佳吾、 坂本幸士、 金谷佳織、 山岨達也
    • Organizer
      第15回日本抗加齢医学会総会
    • Place of Presentation
      福岡国際会議場(福岡県・福岡市)
    • Year and Date
      2015-05-30
    • Related Report
      2015 Annual Research Report
  • [Presentation] タバコ煙が嗅粘膜障害に及ぼす影響と障害の回復に関するモデルマウスを用いた検証2015

    • Author(s)
      上羽瑠美、 近藤健二、 坂本幸士、 菊田周、 藤巻葉子、 金谷佳織、 西嶌大宣、 山岨達也
    • Organizer
      第116回日本耳鼻咽喉科学会
    • Place of Presentation
      東京国際フォーラム(東京都・千代田区)
    • Year and Date
      2015-05-22
    • Related Report
      2015 Annual Research Report
  • [Presentation] 神経変性疾患と嗅覚障害2014

    • Author(s)
      近藤健二
    • Organizer
      第53回日本鼻科学会学術講演会
    • Place of Presentation
      大阪
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] カロリー制限を受ける時期が嗅上皮傷害後の再生過程に与える影響について2014

    • Author(s)
      岩村均、近藤健二、坂本幸士、菊田周、平野真希子、鈴川佳吾、金谷佳織、山岨達也
    • Organizer
      第53回日本鼻科学会学術講演会
    • Place of Presentation
      大阪
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] アリナミンテストの新たな意義 マウスアリナミンテストからのメッセージ2014

    • Author(s)
      菊田周、松本有、坂本幸士、岩村均、西嶌大宣、平野真希子、近藤健二、山岨達也
    • Organizer
      第53回日本鼻科学会学術講演会
    • Place of Presentation
      大阪
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] カロリー制限が嗅上皮障害後の嗅細胞再生に与える影響について2014

    • Author(s)
      岩村均、近藤健二、坂本幸士、菊田周、鈴川佳吾、金谷佳織、山岨達也
    • Organizer
      第115回日本耳鼻咽喉科学会学術講演会
    • Place of Presentation
      福岡
    • Year and Date
      2014-05-15 – 2014-05-17
    • Related Report
      2014 Annual Research Report
  • [Presentation] 嗅上皮におけるアレルギーとウィルス感染の影響 モデルマウスを用いた解析2014

    • Author(s)
      上羽瑠美、近藤健二、上羽悟史、西嶌大宣、菊田周、鈴川佳吾、坂本幸士、山岨達也
    • Organizer
      第115回日本耳鼻咽喉科学会学術講演会
    • Place of Presentation
      福岡
    • Year and Date
      2014-05-15 – 2014-05-17
    • Related Report
      2014 Annual Research Report
  • [Presentation] アリナミンテストの結果に対する病態に基づいた新たな解釈2014

    • Author(s)
      菊田周、松本有、坂本幸士、近藤健二、上羽瑠美、岩村均、籠谷領二、西嶌大宣、鈴川佳吾、平野真希子、山岨達也
    • Organizer
      第115回日本耳鼻咽喉科学会学術講演会
    • Place of Presentation
      福岡
    • Year and Date
      2014-05-15 – 2014-05-17
    • Related Report
      2014 Annual Research Report
  • [Remarks] 東京大学耳鼻咽喉科学教室ホームページ

    • URL

      http://h.u-tokyo.ac.jp/orl/

    • Related Report
      2016 Annual Research Report
  • [Remarks] 東京大学医学部耳鼻咽喉科学教室

    • URL

      http://www.h.u-tokyo.ac.jp/orl/

    • Related Report
      2015 Annual Research Report
  • [Remarks] 東京大学耳鼻咽喉科額教室

    • URL

      http://www.h.u-tokyo.ac.jp/orl/

    • Related Report
      2014 Annual Research Report

URL: 

Published: 2014-04-04   Modified: 2018-03-22  

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