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Role and mechanism of lysophospholipids in functional recovery of spinal cord-injured motor paralysis

Research Project

Project/Area Number 20K09476
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56020:Orthopedics-related
Research InstitutionShinshu University

Principal Investigator

Haniu Hisao  信州大学, 学術研究院医学系, 准教授 (30252050)

Co-Investigator(Kenkyū-buntansha) 植村 健  信州大学, 学術研究院総合人間科学系, 准教授 (00372368)
塚原 完  長崎大学, 医歯薬学総合研究科(薬学系), 准教授 (00529943)
松田 佳和  日本薬科大学, 薬学部, 教授 (20377633)
高橋 淳  信州大学, 学術研究院医学系, 教授 (60345741)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsリゾリン脂質 / 脊髄損傷 / ニューロン / グリア細胞 / 脂肪酸 / 神経再生 / アミロイドタンパク質
Outline of Research at the Start

我々は現在、「神経機能再生促進剤」として特許申請しているプロテアーゼ処理したブタ肝臓分解物(PLDP)による脊椎損傷部の機能回復効果のメカニズム解明のための研究を進めており、PLDP中のリン脂質成分、その中でも特徴的であるリゾリン脂質の神経細胞やグリア細胞でリゾリン脂質毎に多様な反応が観察されている。
本申請では脊髄損傷モデルラットにPLDPを模したリン脂質の投与とその単独成分による効果とその時の代謝を明らかにするとともに、リゾリン脂質の神経関連細胞での作用機序を明らかにする事により、リゾリン脂質を活性本体とした脊髄損傷治癒促進薬の開発を目指す。

Outline of Final Research Achievements

The purpose of this study was to clarify whether lysophospholipid (LPLs) have effects on promoting the healing of motor function paralysis in a mouse model of spinal cord injury (SCI) by the impactor method. Oral administration of porcine liver degradation products has been shown to accelerate the healing of SCI in mice with moderate to severe SCI. In vitro experiments using lysophosphatidylethanolamine, which has been shown to suppress inflammation and promote nerve growth, showed a significant healing-promoting effect only when administered directly to the injured area after injury treatment on a daily basis. Tissue specimens from the injured area showed a decrease in GFAP-positive areas and apoptotic cells in the treated group.

Academic Significance and Societal Importance of the Research Achievements

我々の研究成果は生物由来であるブタ肝臓分解物やその中に含まれるリゾリン脂質の一部に神経修復作用がある事を示している。この成果は外部からの投与のみならず、体内での代謝による運動機能の改善を目指せる可能性をも示している。この研究を発展させることによってリゾリン脂質による神経の保護から修復までの予防薬や治療薬の開発に展開させていきたい。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (8 results)

All 2022 2021 2020

All Journal Article (7 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 6 results) Presentation (1 results)

  • [Journal Article] Lysophospholipids-potent candidates for brain food, protects neuronal cells against α-Synuclein aggregation.2022

    • Author(s)
      Karaki T, Haniu H, Matsuda Y, Tsukahara T.
    • Journal Title

      Biomedicine & Pharmacotherapy

      Volume: 156 Pages: 113891-113891

    • DOI

      10.1016/j.biopha.2022.113891

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Lysophospholipids: A Potential Drug Candidates for Neurodegenerative Disorders2022

    • Author(s)
      Karaki Tatsuya、Haniu Hisao、Matsuda Yoshikazu、Tsukahara Tamotsu
    • Journal Title

      Biomedicines

      Volume: 10 Issue: 12 Pages: 3126-3126

    • DOI

      10.3390/biomedicines10123126

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] リゾリン脂質経口摂取による神経変性疾患の新規創薬基盤開発.2022

    • Author(s)
      塚原完, 唐木達哉, 羽二生久夫, 上芝洸貴, 松田佳和.
    • Journal Title

      Medical Science Digest

      Volume: 48 Pages: 47-9

    • Related Report
      2021 Research-status Report
  • [Journal Article] Abundant oleoyl-lysophosphatidylethanolamine in brain stimulates neurite outgrowth and protects against glutamate toxicity in cultured cortical neurons2021

    • Author(s)
      Kazutoshi Hisano, Hironori Yoshida, Shiori Kawase, Tetsuhiko Mimura, Hisao Haniu, Tamotsu Tsukahara, Taiga Kurihara, Yoshikazu Matsuda, Naoto Saito, Takeshi Uemura
    • Journal Title

      The Journal of Biochemistry

      Volume: 170 Issue: 3 Pages: 327-336

    • DOI

      10.1093/jb/mvab046

    • NAID

      40022722431

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Structurally different lysophosphatidylethanolamine species stimulate neurite outgrowth in cultured cortical neurons via distinct G-protein-coupled receptors and signaling cascades2021

    • Author(s)
      Hisano Kazutoshi、Kawase Shiori、Mimura Tetsuhiko、Yoshida Hironori、Yamada Hiroki、Haniu Hisao、Tsukahara Tamotsu、Kurihara Taiga、Matsuda Yoshikazu、Saito Naoto、Uemura Takeshi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 534 Pages: 179-185

    • DOI

      10.1016/j.bbrc.2020.11.119

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Porcine liver decomposition product-derived lysophospholipids promote microglial activation in vitro2020

    • Author(s)
      Tamotsu Tsukahara, Hisao Haniu, Takeshi Uemura, Yoshikazu Matsuda
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 3748-3748

    • DOI

      10.1038/s41598-020-60781-1

    • NAID

      120006988275

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Therapeutic Potential of Porcine Liver Decomposition Product: New Insights and Perspectives for Microglia-Mediated Neuroinflammation in Neurodegenerative Diseases2020

    • Author(s)
      Tamotsu Tsukahara, Hisao Haniu, Takeshi Uemura & Yoshikazu Matsuda
    • Journal Title

      biomedicines

      Volume: 8 Issue: 11 Pages: 446-446

    • DOI

      10.3390/biomedicines8110446

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] アルツハイマー型認知症の治療及び予防におけるリゾリン脂質の可能性.2022

    • Author(s)
      上芝洸貴, 上田勝也, 馬闖, 泉谷惇, 塚原完, 松田佳和, 齋藤直人, 羽二生久夫.
    • Organizer
      第96回日本薬理学会年会
    • Related Report
      2022 Annual Research Report

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Published: 2020-04-28   Modified: 2024-01-30  

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