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Development of novel method to improve the lipoquality of neurons

Research Project

Project/Area Number 17K19500
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Pharmaceutical Sciences and related fields
Research InstitutionNagoya City University

Principal Investigator

Hattori Mitsuharu  名古屋市立大学, 大学院薬学研究科, 教授 (60272481)

Project Period (FY) 2017-06-30 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2017: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Keywords脂肪酸 / 脳 / リーリン / リポタンパク質 / 精神疾患 / 神経細胞 / リポクオリティ / アルツハイマー病
Outline of Final Research Achievements

Reelin is essential for the development and function of the mammalian brain and the receptors for Reelin, belong to the low-density lipoprotein receptor family, but it is not known whether Reelin is involved in the brain lipid metabolism. We found that Reelin-deficient mouse brain exhibited several compositional changes in phospholipids. The ratio of phospholipids containing one saturated
fatty acid (FA) and one docosahexaenoic acid (DHA) or arachidonic acid (ARA) decreased and the ratio of phospholipids containing one monounsaturated FA and one DHA or ARA increased. The ratio of phospholipids containing Mead acid increased. Therefore, Reelin can upregulate the amount of polyunsaturated fatty acids in the brain, which will help ameliorate neuropsychiatric and neurodegenerative disorders.

Academic Significance and Societal Importance of the Research Achievements

本研究の結果は、「リーリンの機能」「脳の脂肪酸組成」「精神神経疾患の発症」の3者間に今まで漠然と存在した相関を包括的に理解できる可能性を示唆しており、概念的には大きな進歩であると考えている。また、アルツハイマー病などの難治性神経疾患に対する新たな治療法開発の糸口にもなり得るものである。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (38 results)

All 2019 2018 2017

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 2 results) Presentation (34 results) (of which Int'l Joint Research: 9 results)

  • [Journal Article] Reducing ADAMTS-3 Inhibits Amyloid β Deposition in <i>App</i> Knock-in Mouse2019

    • Author(s)
      Yamakage Y, Tsuiji H, Kohno T, Ogino H, Saito T, Saido TC, Hattori M.
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 42 Issue: 3 Pages: 354-356

    • DOI

      10.1248/bpb.b18-00899

    • NAID

      130007606923

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2019-03-01
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reelin deficiency leads to aberrant lipid composition in mouse brain2018

    • Author(s)
      Mizukami T, Ikeda K, Shimanaka Y, Korogi K, Zhou C, Takase H, Tsuiji H, Kono N, Kohno T, Arai H, Arita M, Hattori M.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 505 Issue: 1 Pages: 81

    • DOI

      10.1016/j.bbrc.2018.09.089

    • URL

      https://pure.teikyo.jp/en/publications/20a0cf32-221e-433e-91b9-4f845cd345d4

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genetic and animal model analyses reveal the pathogenic role of a novel deletion of RELN in schizophrenia.2018

    • Author(s)
      Sobue A, Kushima I, Nagai T, Shan W, Kohno T, Aleksic B, Aoyama Y, Mori D, Arioka Y, Kawano N, Yamamoto M, Hattori M, Nabeshima T, Yamada K, Ozaki N.
    • Journal Title

      Sci Rep.

      Volume: 8 Issue: 1 Pages: 13046-13046

    • DOI

      10.1038/s41598-018-31390-w

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Secreted Metalloproteinase ADAMTS-3 Inactivates Reelin2017

    • Author(s)
      Ogino H, Hisanaga A, Kohno T, Kondo Y, Okumura K, Kamei T, Sato T, Asahara H, Tsuiji H, Fukata M, Hattori M
    • Journal Title

      J Neurosci

      Volume: 37 Issue: 12 Pages: 3181-3191

    • DOI

      10.1523/jneurosci.3632-16.2017

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] mRNA様long non-coding RNA であるGomafuの核内繋留機構の解明2019

    • Author(s)
      梅本銀河、上原理加、中川真一、吉田稔、服部光治、築地仁美
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 精神神経疾患の治療を志向した、分解抵抗型リーリンノックインマウスの作製と解析(Establishment of cleavage-resistant Reelin knock-in mouse)2019

    • Author(s)
      奥川英介、荻野ひまり、重信奉文、河野孝夫、大石久史、服部光治
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 筋委縮性側索硬化症ALSの原因となるC9orf72遺伝子変異がもたらす細胞毒性の解析2019

    • Author(s)
      築地仁美、横川美丹衣、服部光治
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] リーリン欠損マウス脳の脂質組成変化と、その意義 に関する解析2019

    • Author(s)
      興梠勝成, 水上智晴, 周春雨, 嶋中雄太, 河野望, 池田和貴, 新井洋由, 有田誠, 服部 光治
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 脳部位特異的にリーリンシグナルを増強させる手法 の開発2019

    • Author(s)
      常浦祐未, 北川佳奈子, 高瀬冴子, 澤幡雅仁, 伊藤教道, 河野孝夫, 服部光治, 永井拓, 山田清文
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] "Reelin C-terminal region regulates hippocampal layer formation "2018

    • Author(s)
      Keisuke Ishii, Takao Kohno, and Mitsuharu Hattori
    • Organizer
      22nd Biennial Meeting of the International Society for Developmental Neuroscience
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Semaphorin 6A-Plexin A2/A4 signaling between neurons and radial glial cells is required for proper positioning of superficial layer neurons in the mouse cerebral cortex2018

    • Author(s)
      Yumiko Hatanaka, Takahiko Kawasaki, Takaya Abe, Go Shioi, Takao Kohno, Mitsuharu Hattori, Akira Sakakibara, Yasuo Kawaguchi, Tatsumi Hirata
    • Organizer
      22nd Biennial Meeting of the International Society for Developmental Neuroscience
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Microinjection of Reelin into the medial prefrontal cortex improves MK801-induced memory impairment2018

    • Author(s)
      Masahito Sawahata, Kanako Kitagawa, Yumi Tsuneura, Taku Nagai, Takao Kohno, Toshitaka Nabeshima, Mitsuharu Hattori, Kiyofumi Yamada
    • Organizer
      The 18th World Congress of Basic and Clinical Pharmacology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ADAMTS-2 mediates the specific cleavage of Reelin in the adult brain2018

    • Author(s)
      Yuko Yamakage, Michinao Kato, Aya Hongo, Himari Ogino, Takumi Ishizuka, Hitomi Tsuiji, Takao Kohno, Mitsuharu Hattori
    • Organizer
      第41回 日本神経科学大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] The interaction between Reelin and its novel binding protein is required for dendrite development of cortical upper-layer neurons.2018

    • Author(s)
      Takao Kohno, Makoto Makino, Keisuke Ishii, Yuki Hirota, Takao Honda, Kazunori Nakajima and Mitsuharu Hattori.
    • Organizer
      第41回 日本神経科学大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] SemaphorinA6 on radial glial cell and PlexinA2/A4 on neuron are required for proper positioning of superficial layer neurons in the cerebral cortex2018

    • Author(s)
      Yumiko Hatanaka, Takahiko Kawasaki, Takaya Abe, Go Shioi, Takao Kohno, Mitsuharu Hattori, Akira Sakakibara, Yasuo Kawaguchi, Tatsumi Hirata
    • Organizer
      第41回 日本神経科学大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Regulation of Reelin functions by proteolytic processing and its significance in brain development and functions2018

    • Author(s)
      MItsuharu Hattori
    • Organizer
      FENS Forum of Neuroscience 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] mRNA様long non-coding RNA であるGomafuの核内繋留機構の解明2018

    • Author(s)
      梅本銀河、中川真一、吉田稔、服部光治、築地仁美
    • Organizer
      第17回次世代を担う若手ファーマ・バイオフォーラム
    • Related Report
      2018 Annual Research Report
  • [Presentation] リーリンシグナルがアルツハイマー病発症に与える影響2018

    • Author(s)
      大嶋智葉、山影祐子、河野孝夫、斎藤貴志、西道隆臣、赤津裕康、松川則之、服部光治
    • Organizer
      第17回次世代を担う若手ファーマ・バイオフォーラム
    • Related Report
      2018 Annual Research Report
  • [Presentation] リーリンシグナルがアルツハイマー病発症に与える影響に関する解析2018

    • Author(s)
      大嶋智葉、山影祐子、河野孝夫、斎藤貴志、西道隆臣、服部光治
    • Organizer
      日本生化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 神経細胞における特定の脂肪酸の生理的意義についての解析2018

    • Author(s)
      興梠勝成、水上智晴、河野孝夫、服部光治
    • Organizer
      日本生化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] TDP-43 accelerates age-dependent degeneration of interneurons2018

    • Author(s)
      Hitomi Tsuiji, Ikuyo Inoue, Asako Furuya, Mari Takeuchi, Yuko Yamakage, Mitsuharu Hattori, Koji Yamanaka
    • Organizer
      12th Brain Research Conference
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 海馬層形成における分泌タンパク質リーリンの機能解明2018

    • Author(s)
      石井圭介、河野孝夫、服部光治
    • Organizer
      日本薬学会東海支部会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 脳の構造と機能に重要なタンパク質リーリンの機能増強マウスの作製と解析2018

    • Author(s)
      奥川英介、荻野ひまり、重信奉文、河野孝夫、大石久史、服部光治
    • Organizer
      日本薬学会東海支部会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Activity of Reelin is regulated by ADMATS metalloproteinases2018

    • Author(s)
      Himari Ogino, Takao Kohno, Yuko Yamakage, Michinao Kato, Eisuke Okugawa, Takumi Ishizuka, Hitomi Tsuiji, Mitsuharu Hattori
    • Organizer
      Gordon Research Conference, Extracellular Proteolysis
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] リーリンと結合する新規分子の探索と生化学的解析2018

    • Author(s)
      牧野誠、河野孝夫、服部光治
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Research-status Report
  • [Presentation] 精神神経疾患の治療を志向した、分解抵抗型リーリンノックインマウスの作製と解析2017

    • Author(s)
      奥川英介、荻野ひまり、河野孝夫、服部光治
    • Organizer
      日本生化学会中部支部会
    • Related Report
      2017 Research-status Report
  • [Presentation] 脳機能に必須なタンパク質リーリンの新規結合分子に関する研究2017

    • Author(s)
      石井圭介、河野孝夫、服部光治
    • Organizer
      第63回 薬学会東海支部会
    • Related Report
      2017 Research-status Report
  • [Presentation] ADAMTS-3 Inactivates Reelin, an Important Regulator of Brain Development and Function2017

    • Author(s)
      Himari Ogino, Takao Kohno, Michinao Kato, Eisuke Okugawa, Mitsuharu Hattori
    • Organizer
      Gordon Research Conference, Matrix Metalloproteinase
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] The functions of Reelin via a novel Reelin-binding protein.2017

    • Author(s)
      Takao Kohno, Hayata Yagyu, Mitsuharu Hattori
    • Organizer
      第40回 日本神経科学大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Secreted Metalloproteinase ADAMTS-3 Inactivates Reelin2017

    • Author(s)
      Himari Ogino, Arisa Hisanaga, Takao Kohno, Eisuke Okugawa, Tomoha Ohsima, Yuta Kondo, Kyoko Okumura, Takana Kamei, Tempei Sato, Hiroshi Asahara, Hitomi Tsuiji, Masaki Fukata, Mitsuharu Hattori
    • Organizer
      第40回 日本神経科学大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 分泌タンパク質リーリンによる、新たな脂質組成制御機構2017

    • Author(s)
      水上智晴、周春雨、池田和貴、高瀬広嗣、河野孝夫、築地仁美、嶋中雄太、新井洋由、有田誠、服部光治
    • Organizer
      第16回次世代を担う若手ファーマ・バイオフォーラム2017
    • Related Report
      2017 Research-status Report
  • [Presentation] 生後脳におけるリーリン特異的分解に寄与する酵素の解明2017

    • Author(s)
      山影祐子、加藤路尚、荻野ひまり、石塚拓巳、河野孝夫、服部光治
    • Organizer
      第16回次世代を担う若手ファーマ・バイオフォーラム2017
    • Related Report
      2017 Research-status Report
  • [Presentation] ADAMTS-3は大脳皮質と海馬におけるリーリン機能を負に制御する2017

    • Author(s)
      荻野ひまり、久永有紗、近藤佑多、河野孝夫、築地仁美、服部光治
    • Organizer
      第16回次世代を担う若手ファーマ・バイオフォーラム2017
    • Related Report
      2017 Research-status Report
  • [Presentation] 精神神経疾患の治療を志向した、分解抵抗型リーリンノックインマウスの作製と解析2017

    • Author(s)
      奥川英介、荻野ひまり、河野孝夫、服部光治
    • Organizer
      第16回次世代を担う若手ファーマ・バイオフォーラム2017
    • Related Report
      2017 Research-status Report
  • [Presentation] Regulation of Reelin function by specific proteolysis2017

    • Author(s)
      M. HATTORI, H. OGINO, E. OKUGAWA, Y. YAMAKAGE, T. KOHNO
    • Organizer
      Society for Neuroscience (SFN)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Contribution of ADMATS family members to Reelin inactivation in the postnatal brain2017

    • Author(s)
      M. KATO, T. KOHNO, M. HATTORI
    • Organizer
      Society for Neuroscience (SFN)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 脳機能改善を目指した、巨大分泌タンパク質リーリンの活性制御2017

    • Author(s)
      河野孝夫、服部光治
    • Organizer
      ConBio2017
    • Related Report
      2017 Research-status Report
  • [Presentation] To clarify how Reelin affects the lipid compositions of neurons2017

    • Author(s)
      Katsunari Korogi, Tomoharu Mizukami, Chunyu Zhou, Takao Kohno, Fumiyoshi Yamazaki, Katsuya Kabashima, Yuta Shimanaka, Kazutaka Ikeda, Hiroyuki Arai, Makoto Arita, Mitsutoshi Setou, Mitsuharu Hattori
    • Organizer
      ConBio2017
    • Related Report
      2017 Research-status Report

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Published: 2017-07-21   Modified: 2020-03-30  

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