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Development of animal models for the itchy eyes through the control of central nervous system

Research Project

Project/Area Number 19K06475
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 42040:Laboratory animal science-related
Research InstitutionNational Institute of Genetics

Principal Investigator

Takanami Keiko  国立遺伝学研究所, 遺伝形質研究系, 助教 (70578830)

Co-Investigator(Kenkyū-buntansha) 小出 剛  国立遺伝学研究所, 遺伝形質研究系, 准教授 (20221955)
坂本 浩隆  岡山大学, 自然科学研究科, 准教授 (20363971)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords眼の痒み / 結膜炎 / モデル動物作製 / 種差 / 系統差 / ガストリン放出ペプチド受容体 / 標的細胞ノックアウト法 / 行動解析 / 掻痒症 / 行動特性 / モデル動物開発 / 遺伝子改変マウス / 痒み / 掻き行動 / 遺伝子改変動物 / ラット / マウス / 多系統
Outline of Research at the Start

環境汚染やライフスタイルの変化により、多くの眼疾患の共通症状である結膜炎による目の掻痒症が増加している。慢性化すると難治性掻痒症となり、深刻な眼の二次疾患を導くが、これまで目の痒み(かゆみ)に対する治療法は末梢の結膜における炎症抑制が主であった。これは、結膜炎モデル動物の作出が難しく、痒み独自の中枢性分子基盤が不明だったからだと考えられる。そこで、本研究では、多系統のマウスを用い、ヒトの病態に近い結膜炎モデルを開発し、痒み中枢の制御機構の解析を行い、結膜炎掻痒症の病態解明に繋げることを目的とする。

Outline of Final Research Achievements

Environmental pollution and lifestyle changes increased the eye disease with itchy eyes including pollen hypersensitivity. Itchy eyes with continuous scratching leads to further exacerbation of eye symptoms and serious secondary eye disease. However, treatment for eye itch has been primarily based on suppression of inflammation in the peripheral conjunctiva, because the molecular basis for the transmission of itchy eyes was unknown. In this study, we found a model of conjunctivitis similar to the human condition and a neural circuit that transmits itchy eyes using rodent animal models. These study will lead to further elucidation of the pathogenesis of itchy eyes.

Academic Significance and Societal Importance of the Research Achievements

結膜炎による眼の痒みを抑えるための中枢制御領域として、下部延髄がひとつの重要な拠点であることが分かり、この領域におけるガストリン放出ペプチド受容体発現細胞の活性を抑えることで、眼の痒みを制御できる可能性が示唆された。また、齧歯類モデル動物であるラットとマウスを用いた解析から、眼の痒みの感受性に対する大きな種差や系統差がみられたことから、モデル動物の比較解析が新たなヒトの結膜炎掻痒症を反映するモデル動物作製に繋がることが示唆された。

Report

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

    (31 results)

All 2022 2021 2020 2019 Other

All Int'l Joint Research (4 results) Journal Article (5 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (22 results) (of which Int'l Joint Research: 7 results,  Invited: 8 results)

  • [Int'l Joint Research] University of California, Davis(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] University of Oxford(英国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] University of California, Davis(米国)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] University of California, Davis(米国)

    • Related Report
      2019 Research-status Report
  • [Journal Article] Oxytocin Influences Male Sexual Activity via Non-synaptic Axonal Release in the Spinal Cord2021

    • Author(s)
      Oti Takumi、Satoh Keita、Uta Daisuke、Nagafuchi Junta、Tateishi Sayaka、Ueda Ryota、Takanami Keiko、Young Larry J.、Galione Antony、Morris John F.、Sakamoto Tatsuya、Sakamoto Hirotaka
    • Journal Title

      Current Biology

      Volume: 31 Issue: 1 Pages: 103-114

    • DOI

      10.1016/j.cub.2020.09.089

    • NAID

      120007168224

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The gastrin-releasing peptide/bombesin system revisited by a reverse-evolutionary study considering Xenopus2021

    • Author(s)
      Hirooka Asuka、Hamada Mayuko、Fujiyama Daiki、Takanami Keiko、Kobayashi Yasuhisa、Oti Takumi、Katayama Yukitoshi、Sakamoto Tatsuya、Sakamoto Hirotaka
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 13315-13315

    • DOI

      10.1038/s41598-021-92528-x

    • NAID

      120007120048

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Estrogens influence female itch sensitivity via the spinal gastrin-releasing peptide receptor neurons2021

    • Author(s)
      Keiko Takanami, Daisuke Uta, Ken Ichi Matsuda, Mitsuhiro Kawata, Earl Carstens, Tatsuya Sakamoto, Hirotaka Sakamoto
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 118 Issue: 31

    • DOI

      10.1073/pnas.2103536118

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Variation of pro‐vasopressin processing in parvocellular and magnocellular neurons in the paraventricular nucleus of the hypothalamus: Evidence from the vasopressin‐related glycopeptide copeptin2020

    • Author(s)
      Kawakami Natsuko、Otubo Akito、Maejima Sho、Talukder Ashraf H.、Satoh Keita、Oti Takumi、Takanami Keiko、Ueda Yasumasa、Itoi Keiichi、Morris John F.、Sakamoto Tatsuya、Sakamoto Hirotaka
    • Journal Title

      Journal of Comparative Neurology

      Volume: 529 Issue: 7 Pages: 1372-1390

    • DOI

      10.1002/cne.25026

    • NAID

      120006890023

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Detection and Characterization of Estrogen Receptor Beta Expression in the Brain with Newly Developed Transgenic Mice2020

    • Author(s)
      Shoko Sagoshi, Sho Maejima, Masahiro Morishita, Satoshi Takenawa, Akito Otubo, Keiko Takanami, Tatsuya Sakamoto, Hirotaka Sakamoto, Shinji Tsukahara, Sonoko Ogawa
    • Journal Title

      Neuroscience

      Volume: 438 Pages: 182-197

    • DOI

      10.1016/j.neuroscience.2020.04.047

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 女性ホルモンが痒みの感受性を調節するメカニズム2022

    • Author(s)
      高浪景子
    • Organizer
      奈良女子大学ライフサイエンスセミナー
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 所内共同研究に基づく透過型電子顕微鏡解析支援の取り組み2022

    • Author(s)
      大石あかね、高浪景子、小出剛
    • Organizer
      第33回生物学技術研究会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ガストリン放出ペプチド神経系による体性感覚調節機構2022

    • Author(s)
      高浪景子、坂本浩隆
    • Organizer
      第127回日本解剖学会総会・全国学術集会 シンポジウム「信号伝達分子として働く神経ペプチドの多彩な作用を理解する」
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 痒みの神経伝達基盤 ―疾患モデル動物を用いた検討―2021

    • Author(s)
      高浪景子, 小出 剛, 坂本浩隆
    • Organizer
      第94回日本内分泌学会学術総会 シンポジウム「神経内分泌研究のアップデート」
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] マウスの知覚閾値の系統差2021

    • Author(s)
      高浪景子, 小出剛
    • Organizer
      第68回日本実験動物学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] マウスの家畜化に伴う腸内微生物叢の変化2021

    • Author(s)
      Bhim B. Biswa、高浪景子,豊田敦,森宙史,黒川顕, 小出 剛
    • Organizer
      第68回日本実験動物学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 齧歯類における痒み閾値の種差と系統差2021

    • Author(s)
      高浪景子, 小出剛
    • Organizer
      第44回日本神経科学大会 Neuro 2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Affect of Esr1 polymorphisms in maternal behavior in mouse2021

    • Author(s)
      Lalitha Devi, Akira Tanave, Yuji Imai, Keiko Takanami, Tsuyoshi Koide
    • Organizer
      第44回日本神経科学大会 Neuro 2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Histochemical challenges to the itch neurotransmission and evolution2021

    • Author(s)
      Keiko Takanami
    • Organizer
      International Federation of Societies for Histochemistry and Cytochemistry, IFSHC Workshop 2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 高浪景子, 歌大介, 松田賢一, 河田光博, Earl Carstens, 坂本竜哉, 坂本浩隆2021

    • Author(s)
      17β-エストラジオールによる痒み閾値調節
    • Organizer
      第47回日本神経内分泌学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Affect of Esr1 polymorphisms in maternal behavior in mouse2021

    • Author(s)
      Lalitha Devi, Keiko Takanami, Akira Tanave, Yuji Imai, Tsuyoshi Koide
    • Organizer
      第47回日本神経内分泌学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Affect of Esr1 polymorphisms in maternal behavior in mouse2021

    • Author(s)
      Lalitha Devi, Keiko Takanami ,Akira Tanave, Yuji Imai, Tsuyoshi Koide
    • Organizer
      Neuroscience 2021- 50th Annual Meeting- Society for Neuroscience
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 野生由来系統・実験系統・愛玩系統マウスにおける知覚閾値の系統差2021

    • Author(s)
      高浪景子、小出剛
    • Organizer
      国立遺伝学研究所 行動遺伝学研究会 「家畜化機構の解明」
    • Related Report
      2021 Annual Research Report
  • [Presentation] かゆみの分子および機能進化 ―形態学からのアプローチー2021

    • Author(s)
      高浪景子
    • Organizer
      第126回日本解剖学会総会・全国学術集会・第98回日本生理学会大会合同大会・公募シンポジウム「皮膚感覚の処理機構とその応用」
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 女性ホルモンによるかゆみ閾値調節2020

    • Author(s)
      高浪景子
    • Organizer
      環境医学研究所・順天堂かゆみ研究センター 第6回学術シンポジウム ~難治性かゆみの克服を目指して~
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] Chronic stress affects itch sensitivity and male sexual function in rats2019

    • Author(s)
      K Takanami, M Morishita, T Sakamoto, H Sakamoto
    • Organizer
      10th World Congress on Itch
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Molecular and functional evolutionary analysis of itch focused on the gastrin-releasing peptide system in vertebrate2019

    • Author(s)
      K Takanami, D Fujiyama, A Hirooka, H Sakamoto
    • Organizer
      THE 48th NAITO CONFERENCE on Integrated Sensory Sciences―Pain, Itch, Smell and Taste
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 遺伝子改変動物を用いた難治性掻痒症におけるペプチドニューロンの機能解析2019

    • Author(s)
      高浪景子
    • Organizer
      第46回日本神経内分泌学会学術集会、若手助成金成果報告
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 組織学解析による痒み伝達機構の可視化2019

    • Author(s)
      高浪景子
    • Organizer
      第60回日本組織細胞化学会総会・学術集会、シンポジウム 女性研究者セッション~組織細胞化学研究の魅力を語る~
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 脳が引き起こす痒み2019

    • Author(s)
      高浪景子、Amanda Nguyen、小出 剛
    • Organizer
      第31回日本行動神経内分泌研究会
    • Related Report
      2019 Research-status Report
  • [Presentation] Effects of sociality on the social contagious behavior2019

    • Author(s)
      K Takanami, O Yakimenko, H Nagayama, T Koide
    • Organizer
      The 42th Annual Meeting of the Japan Neuroscience Society
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] マウスの系統間における痒覚および痛覚閾値の比較解析2019

    • Author(s)
      高浪景子、小出剛
    • Organizer
      第66回日本実験動物学会総会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2024-01-30  

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