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New development of clarification and control on mechanism of neurogenesis of fluorescent enteric neurons responding to stimuli.

Research Project

Project/Area Number 15H03057
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Rehabilitation science/Welfare engineering
Research InstitutionNara Medical University

Principal Investigator

Takaki Miyako  奈良県立医科大学, 医学部, 研究員 (00033358)

Co-Investigator(Kenkyū-buntansha) 國安 弘基  奈良県立医科大学, 医学部, 教授 (00253055)
中井 淳一  埼玉大学, 理工学研究科, 教授 (80237198)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2017: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2016: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2015: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Keywordsリハビリテーション医学 / Caイメージング / セロトニン4受容体 / 腸壁内神経 / 神経再生・新生 / 腸管切離吻合モデル / GCaMPトランスジェニックマウス / 2光子顕微鏡 / カルシウムイメージング / 5-HT4 受容体 / 再生医学 / リハビリテーション
Outline of Final Research Achievements

The reconstruct of impaired enteric neural circuits at the thick granulation tissue at anastomosis in small intestine of H-line: Thy1 promoter GFP mouse was observed by two-photon microscopy a week after drinking a 5-HT4-receptor agonist, mosapride citrate (MOS) 100 microM solution.
In Thy1-promoter YFP mouse after gut transection and anastomosis, the fetal brain-derived neural stem cells (NSC) with red fluorescent cell linker were transplanted from the tail vein. 5-HT4 receptor-mediated facilitation of neurogenesis was confirmed by clear three-dimensional in vivo imaging of newborn enteric neurons generated from enteric neural progenitors (host NSC; green fluorescence) and those from transplant NSC (red fluorescence). The facilitating effect of MOS and the distribution of new neurons were similar between the transplant and host NSC. Finally, though preliminary, we succeeded in in vivo Ca2+ imaging of myenteric neuronal activity in the normal ileum of Thy1-G6-mCherry transgenic mouse.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (26 results)

All 2018 2017 2016 2015

All Journal Article (8 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 8 results,  Open Access: 7 results,  Acknowledgement Compliant: 4 results) Presentation (17 results) (of which Int'l Joint Research: 2 results,  Invited: 4 results) Book (1 results)

  • [Journal Article] Intermittent calorie restriction enhances epithelial- mesenchymal transition through alteration of energy metabolism in a mouse tumor model.2018

    • Author(s)
      Kusuoka O, Fujiwara-Tani R, Nakashima C, Fujii K, Ohmori H, Mori T, Kishi S, Miyagawa Y, Goto K, Kawahara I, Kuniyasu H
    • Journal Title

      Int J Oncol

      Volume: 52 Pages: 413-423

    • DOI

      10.3892/ijo.2017.4229

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Pancreatic adenocarcinoma upregulated factor has oncogenic functions in oral squamous cell carcinoma.2017

    • Author(s)
      Sasahira T, Kurihara M, Nishiguchi Y, Nakashima C, Kirita T, Kuniyasu H.
    • Journal Title

      Histopathol

      Volume: in press Issue: 4 Pages: 539-48

    • DOI

      10.1111/his.13097

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fatty acids induce stemness in the stromal cells of a CT26 mouse tumor model2017

    • Author(s)
      Kawahara I, Mori T, Goto K, Fujii K, Ohmori H, Fujiwara-Tani R, Kuniyasu H
    • Journal Title

      Pathobiol

      Volume: in press Issue: 5 Pages: 237-242

    • DOI

      10.1159/000471854

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Activation of 5-HT4-receptors facilitates neurogenesis from transplanted neural stem cells in the anastomotic ileum.2016

    • Author(s)
      Goto K, Kawahara I, Inada H, Misawa H, Kuniyasu H, Nabekura J, Takaki M.
    • Journal Title

      J Physiol Sci,

      Volume: 66 Issue: 1 Pages: 67-76

    • DOI

      10.1007/s12576-015-0396-1

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Activation of 5-HT<sub>4</sub> receptors facilitates neurogenesis of injured enteric neurons at an anastomosis in the lower gut2015

    • Author(s)
      Takaki M, Goto K, Kawahara I, Nabekura J
    • Journal Title

      Journal of Smooth Muscle Research

      Volume: 51 Issue: 0 Pages: 82-94

    • DOI

      10.1540/jsmr.51.82

    • NAID

      130005130210

    • ISSN
      0916-8737, 1884-8796
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Characterizations of the α1-adrenoceptor subtypes mediating contractions of the human internal anal sphincter.2015

    • Author(s)
      Owaki H, Sadahiro S, Takaki M
    • Journal Title

      J Pharmacol Sci

      Volume: 127 Issue: 4 Pages: 424-429

    • DOI

      10.1016/j.jphs.2015.02.016

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of ethanol on mouse embryonic stem cell differentiation.2015

    • Author(s)
      Yamashita A, Asahi J, Takaki M, Nakashima T, Kamiwada K, Watanabe S, Murakami D, Hirano T.
    • Journal Title

      Int J Pharm Pharmaceut Sci,

      Volume: 7 Pages: 274-278

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A protein tyrosine kinase receptor, c-RET signaling pathway contributes to the enteric neurogenesis induced by a 5-HT4 receptor agonist at an anastomosis after transection of the gut in rodents.2015

    • Author(s)
      Goto K, Kawahara I, Kuniyasu H, Takaki M
    • Journal Title

      J Physiol Sci

      Volume: 未定 Issue: 4 Pages: 377-383

    • DOI

      10.1007/s12576-015-0377-4

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Dose-dependent energy-saving action of a new myosin activator, omecamtiv mecarbil on LV mechanical work and energetics.2018

    • Author(s)
      Obata Koji, Morita Hironobu, Takaki Miyako
    • Organizer
      第95回日本生理学会大会, サンポートホール高松
    • Related Report
      2017 Annual Research Report
  • [Presentation] Auto-regulation of osteoblast mechanosensitivity via P2Y2 receptor.2018

    • Author(s)
      Asada Keiji, Morimoto Yasuhiko, Okumura Yu, Takaki Miyako
    • Organizer
      第95回日本生理学会大会, サンポートホール高松
    • Related Report
      2017 Annual Research Report
  • [Presentation] Symposium 35 Cardica mechanics and energetics. 1-3 Challenge mechanoenergetics analysis with new technology.2017

    • Author(s)
      Obata K, Abe C, Morita H, Takaki M.
    • Organizer
      第94回日本生理学会大会
    • Place of Presentation
      アクトシテイ浜松
    • Year and Date
      2017-03-30
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Ca2+ release activated Ca2+ channel does not contribute to intracellular signal transduction of normal mouse fibroblast-like synoviocytes induced by mechanical stimulation.2017

    • Author(s)
      Asada K, Okumura Y, Morimoto Y, Takaki M.
    • Organizer
      第94回日本生理学会大会
    • Place of Presentation
      アクトシテイ浜松
    • Year and Date
      2017-03-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] S3 腸管神経の発生・障害・再生研究の最前線 1S3-3 外科的に切断した腸壁内神経の5-HT4受容体活性化による再生・新生2017

    • Author(s)
      高木 都
    • Organizer
      第122回日本解剖学会総会・全国学術集会シンポジウム
    • Place of Presentation
      長崎大学坂本キャンパス良順会館専斎ホール
    • Year and Date
      2017-03-28
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Signal transmission via purinergic receptors to sensory nerved from mechaniscal stimulation of bone or joints.2017

    • Author(s)
      Asada K, Okumura Y, Morimoto Y, Takaki M
    • Organizer
      4th Congress of ISAN (International Society of Autonomic Neuroscience) 2017 in Nagoya, Japan
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 左心室の力学的エネルギー学的性質における新規のミオシンアクチベーター, omecamtiv mecarbilの効果2016

    • Author(s)
      小畑孝二, 森田啓之, 高木 都
    • Organizer
      第26回日本病態生理学会大会
    • Place of Presentation
      金沢医科大学医学教育棟
    • Year and Date
      2016-08-07
    • Related Report
      2016 Annual Research Report
  • [Presentation] 骨芽細胞と神経細胞の共培養実験系におけるP2Y2Rを介する骨芽細胞内制御系の関与2016

    • Author(s)
      森本安彦, 浅田啓嗣, 奥村 裕, 高木 都
    • Organizer
      第26回日本病態生理学会大会
    • Place of Presentation
      金沢医科大学医学教育棟
    • Year and Date
      2016-08-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] マウス滑膜細胞のメカニカルストレスに対する細胞内カルシウムを介するシグナル伝達の解析2016

    • Author(s)
      浅田啓嗣, 奥村 裕, 森本安彦, 高木 都
    • Organizer
      第26回日本病態生理学会大会
    • Place of Presentation
      金沢医科大学医学教育棟
    • Year and Date
      2016-08-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] Positive and negative inotropic effects of left ventricular mechano-energetics in hypothermic and hyperthermic rat hearts.2016

    • Author(s)
      Obata K, Morita H, Takaki M.
    • Organizer
      Experimental Biology
    • Place of Presentation
      San Diego, CA
    • Year and Date
      2016-04-02
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Mechanism of positive inotropic action of a new myosin activator, omecamtiv mecarbil on LV mechanical work and energetics.2016

    • Author(s)
      Koji Obata, Hironobu Morita, Miyako Takaki
    • Organizer
      第93回日本生理学会大会
    • Place of Presentation
      札幌コンベンションセンター
    • Year and Date
      2016-03-24
    • Related Report
      2015 Annual Research Report
  • [Presentation] Calcium imaging of dorsal root ganglionic neurons and fibroblast-like synoviocytes to mechanical stimulation in co-culture system.2016

    • Author(s)
      Keiji Asada, Yasuhiko Morimoto, Yu Okumura, Miyako Takaki
    • Organizer
      第93回日本生理学会大会
    • Place of Presentation
      札幌コンベンションセンター
    • Year and Date
      2016-03-23
    • Related Report
      2015 Annual Research Report
  • [Presentation] 5-HT4受容体活性化による損傷した腸壁内神経の再生・新生2015

    • Author(s)
      高木 都, 後藤 桂, 川原 勲, 鍋倉淳一
    • Organizer
      第57回日本平滑筋学会総会
    • Place of Presentation
      山口大学小串キャンパス総合研究棟
    • Year and Date
      2015-08-27
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 5-HT4受容体活性化による損傷腸壁内神経の新生促進効果における受容体型チロシンキナーゼc-RET情報伝達経路の関与2015

    • Author(s)
      高木 都,後藤 桂, 川原 勲, 國安弘基
    • Organizer
      第25回日本病態生理学会大会
    • Place of Presentation
      愛媛大学城北キャンパス
    • Year and Date
      2015-08-02
    • Related Report
      2015 Annual Research Report
  • [Presentation] 共培養系による滑膜細胞・神経細胞間相互作用の解析2015

    • Author(s)
      浅田啓嗣, 森本安彦, 高木 都
    • Organizer
      第25回日本病態生理学会大会
    • Place of Presentation
      愛媛大学城北キャンパス
    • Year and Date
      2015-08-02
    • Related Report
      2015 Annual Research Report
  • [Presentation] 骨芽細胞と神経細胞の共培養実験系における相互作用について2015

    • Author(s)
      森本安彦, 浅田啓嗣, 高木 都
    • Organizer
      第25回日本病態生理学会大会
    • Place of Presentation
      愛媛大学城北キャンパス
    • Year and Date
      2015-08-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] 左心室力学的エネルギー学的性質へのミオシンアクチベーターとSERCAアクチベーターの効果2015

    • Author(s)
      小畑孝二, 森田啓之, 高木 都
    • Organizer
      第25回日本病態生理学会大会
    • Place of Presentation
      愛媛大学城北キャンパス
    • Year and Date
      2015-08-01
    • Related Report
      2015 Annual Research Report
  • [Book] Chapter 12 Enteric neurogenesis In Physiology of the Gastrointestinal tract, 6th edition2018

    • Author(s)
      Takaki M
    • Total Pages
      1812
    • Publisher
      Elsevier Academic Press
    • ISBN
      9780128099544
    • Related Report
      2017 Annual Research Report

URL: 

Published: 2015-04-16   Modified: 2019-03-29  

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