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Physiological role of arginine vasopressin released from RGCs on circadian rhythm and psychiatry function

Research Project

Project/Area Number 19K06939
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 46030:Function of nervous system-related
Research InstitutionUniversity of Fukui

Principal Investigator

Tsuji Takahiro  福井大学, 学術研究院医学系部門(附属病院部), 助教 (40787389)

Co-Investigator(Kenkyū-buntansha) 辻 知陽  金沢大学, 子どものこころの発達研究センター, 協力研究員 (00523490)
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: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsバソプレシン / 網膜神経節細胞 / 視交叉上核 / 概日リズム / 社会的時差ぼけ / 睡眠障害 / 光同期 / 発達障害 / iDTR / adeno associated virus / 時差ぼけ / DREADD / AAV2 / 光療法 / 精神機能 / 自閉症 / 社会認識
Outline of Research at the Start

時差ぼけは体内時計と外界の時計がずれることで起こるリズム障害である。バソプレシン(AVP)は時差ぼけからの再同期を阻害するが、AVPによる時差ぼけ制御機構は解明されていない。申請者は、AVPが内因性光感受性網膜神経節細胞に存在することを発見した。そこで、網膜特異的AVP変異マウスを作成し、その行動を解析する研究を計画した。本研究によりAVPによる時差ぼけからの概日リズム再同期の分子機序を明らかにする。

Outline of Final Research Achievements

We generated genetically engineered mouse models by two methods, to elucidate the physiological significance of vasopressin (AVP) signaling in the retina. First, we aimed to manipulate AVP signaling specifically in the retina by intravitreal administration of adeno-associated virus (AAV) to mice expressing Cre recombinase in AVP cells (AVP-Cre). Among several candidate viruses, AAV2-CAGGS-Flex-EGFP was found to infect the retina most frequently but about 20% at best in the infection efficiency. Second, we generated mice that express AVP-specific diphtheria receptors. Intraperitoneal and intravitreal injection of diphtheria toxin into these mice resulted in a partial reduction of AVP cells in the brain and retina in the former, and elimination of most intraretinal AVP cells in the latter.

Academic Significance and Societal Importance of the Research Achievements

バソプレシン(AVP)は、網膜や嗅覚系などから脳内に幅広く発現する分子であり、体内の水分ホメオスタシスの維持から概日リズムや社会性などの行動にも関係する分子である。しかし、それら行動の分子機構については解明されていない。申請者の作成した、ジフテリア毒素注入による部位特異的AVP細胞除去システムは、効率的に部位特異的にAVP細胞を除去できる実験系である。この実験系による網膜AVPの生理的機能解明は、概日リズム障害の眼局所投与薬の開発につながることが期待される。さらに、部位特異的なAVP細胞除去によりAVPの多様な生理的役割の脳内分子機序解明にも応用することができる。

Report

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

    (19 results)

All 2022 2021 2020 2019

All Journal Article (10 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 8 results,  Open Access: 5 results) Presentation (8 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Book (1 results)

  • [Journal Article] The Mechanism of Glaucomatous Optic Neuropathy Caused by Alteration of Cerebrospinal Fluid(intracranial)Pressure2022

    • Author(s)
      辻 隆宏
    • Journal Title

      Neuro-Ophthalmology Japan

      Volume: 39 Issue: 1 Pages: 10-17

    • DOI

      10.11476/shinkeiganka.39.10

    • ISSN
      0289-7024, 2188-2002
    • Year and Date
      2022-03-25
    • Related Report
      2021 Annual Research Report
  • [Journal Article] Intermitochondrial signaling regulates the uniform distribution of stationary mitochondria in axons2022

    • Author(s)
      Matsumoto Nozomu、Hori Ikuma、Kajita Masashi K.、Murase Tomoya、Nakamura Wataru、Tsuji Takahiro、Miyake Seiji、Inatani Masaru、Konishi Yoshiyuki
    • Journal Title

      Molecular and Cellular Neuroscience

      Volume: 119 Pages: 103704-103704

    • DOI

      10.1016/j.mcn.2022.103704

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oral Supplementation with L-Carnosine Attenuates Social Recognition Deficits in CD157KO Mice via Oxytocin Release2022

    • Author(s)
      Tsuji Takahiro、Furuhara Kazumi、Gerasimenko Maria、Shabalova Anna、Cherepanov Stanislav M、Minami Kana、Higashida Haruhiro、Tsuji Chiharu
    • Journal Title

      Nutrients

      Volume: 14 Issue: 4 Pages: 803-803

    • DOI

      10.3390/nu14040803

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oxytocin administration modulates the complex type of ultrasonic vocalisation of mice pups prenatally exposed to valproic acid2021

    • Author(s)
      Tsuji Takahiro、Mizutani Ryuko、Minami Kana、Furuhara Kazumi、Fujisaku Tomoaki、Pinyue Fu、Jing Zhong、Tsuji Chiharu
    • Journal Title

      Neuroscience Letters

      Volume: 758 Pages: 135985-135985

    • DOI

      10.1016/j.neulet.2021.135985

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 嗅覚系・視覚伝達系における神経ペプチド・バソプレシンの脳内での働きの解明をめざして2021

    • Author(s)
      辻 隆宏、辻 知陽
    • Journal Title

      The Journal of Child & Brain Development

      Volume: 12 Issue: 1 Pages: 47-52

    • DOI

      10.34572/jcbd.12.1_47

    • NAID

      130008104069

    • ISSN
      2185-1417, 2435-8819
    • Related Report
      2021 Annual Research Report
  • [Journal Article] Oxytocin Ameliorates Maternal Separation-Induced Ultrasonic Vocalisation Calls in Mouse Pups Prenatally Exposed to Valproic Acid2020

    • Author(s)
      Chiharu Tsuji, Tomoaki Fujisaku, Takahiro Tsuji
    • Journal Title

      Journal of Neuroendocrinology

      Volume: ahead of print Issue: 4

    • DOI

      10.1111/jne.12850

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] A monoclonal antibody raised against a synthetic oxytocin peptide stains mouse hypothalamic neurones2020

    • Author(s)
      Kogami Yuji、Tsuji Takahiro、Tsuji Chiharu、Yokoyama Shigeru、Furuhara Kazumi、Lopatina Olga、Shabalova Anna、Salmina Alla B.、Watanabe Yumi、Hattori Tsuyoshi、Nishimori Katsuhiko、Kodama Kota、Higashida Haruhiro
    • Journal Title

      Journal of Neuroendocrinology

      Volume: - Issue: 4

    • DOI

      10.1111/jne.12815

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Participatory Art Activities Increase Salivary Oxytocin Secretion of ASD Children2020

    • Author(s)
      Tanaka Sanae、Komagome Aiko、Iguchi-Sherry Aya、Nagasaka Akiko、Yuhi Teruko、Higashida Haruhiro、Rooksby Maki、Kikuchi Mitsuru、Arai Oko、Minami Kana、Tsuji Takahiro、Tsuji Chiharu
    • Journal Title

      Brain Sciences

      Volume: 10 Issue: 10 Pages: 680-680

    • DOI

      10.3390/brainsci10100680

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Oxytocin induced epithelium-mesenchimal transition through Rho-ROCK pathway in ARPE-19 cells, a human retinal pigmental cell line2020

    • Author(s)
      Tsuji Takahiro、Inatani Masaru、Tsuji Chiharu、Cheranov Stanislav M.、Kadonosono Kazuaki
    • Journal Title

      Tissue and Cell

      Volume: 64 Pages: 101328-101328

    • DOI

      10.1016/j.tice.2019.101328

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Coding of odors in the anterior olfactory nucleus2019

    • Author(s)
      Tsuji Takahiro、Tsuji Chiharu、Lozic Maja、Ludwig Mike、Leng Gareth
    • Journal Title

      Physiological Reports

      Volume: 7 Issue: 22

    • DOI

      10.14814/phy2.14284

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 脳圧と眼圧の関係について2021

    • Author(s)
      辻 隆宏
    • Organizer
      第125回日本眼科学会総会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] オキシトシンはバルプロ酸暴露マウス仔の母親分離による仔の超音波発声のcomplexタイプを変調する。2021

    • Author(s)
      辻 隆宏、辻 知陽
    • Organizer
      第64回日本神経化学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Coding of odors in the anterior olfactory nucleus2020

    • Author(s)
      Takahiro Tsuji
    • Organizer
      第63回日本神経化学会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] Oxytocin ameliorates maternal separation-induced ultrasonic vocalization calls in mouse pups prenatally exposed to valproic acid2020

    • Author(s)
      Chiharu Tsuji, Takahiro Tsuji
    • Organizer
      第63回日本神経化学会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] Coding of odors in the anterior olfactory nucleus2020

    • Author(s)
      Takahiro Tsuji
    • Organizer
      New Frontier in Neuroscience 2020 International Symposium on Neural Development, Regeneration & Diseases
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Reduced emission of ultrasonic vocalization in the valproic acid exposed pups2019

    • Author(s)
      Chiharu Tsuji, Tomoaki Fujisaku, Takahiro Tsuji
    • Organizer
      13th World Congress of Neurohypophysial Hormone (WCNH2019)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Establishment of female social behavioral paradigm to detect social deficit in the valproic acid-induced mouse model of autism.2019

    • Author(s)
      Chiharu Tsuji, Pinyue Fu, Zing Zhong, Takahiro Tsuji
    • Organizer
      第42回日本神経科学・神経化学合同大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Impairment of pup Ultrasonic vocalization ofvalproic-acid induced mouse model of autism2019

    • Author(s)
      Takahiro Tsuji,Tomoaki Fujisaku, Takahiro Tsuji
    • Organizer
      第42回日本神経科学・神経化学合同大会
    • Related Report
      2019 Research-status Report
  • [Book] 【すべて見せます!患者説明・同意書マニュアル】神経眼科 視神経炎に対するステロイドパルス治療(解説/特集)2020

    • Author(s)
      辻 隆宏
    • Total Pages
      2
    • Publisher
      臨床眼科
    • Related Report
      2020 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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