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Molecular basis of neural cell response to the nutritional intake of fatty acids during development

Research Project

Project/Area Number 19H04026
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 59040:Nutrition science and health science-related
Research InstitutionTohoku University

Principal Investigator

OWADA Yuji  東北大学, 医学系研究科, 教授 (20292211)

Co-Investigator(Kenkyū-buntansha) 香川 慶輝  東北大学, 医学系研究科, 助教 (30728887)
宮崎 啓史  東北大学, 医学系研究科, 助教 (90803867)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2021: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2020: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2019: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Keywordsアストロサイト / ニューロン / 脂肪酸 / ミトコンドリア / オレイン酸 / エピゲノム / 脂肪酸結合タンパク質 / 脂質 / 長鎖脂肪酸 / ミクログリア / 脂肪酸結合タンパク質3型 / リンパ球 / マウス / 発達期栄養 / グリア―ニューロン連関 / 髄鞘形成 / 脂肪酸栄養 / 悪性グリオーマ / 胎児期栄養
Outline of Research at the Start

脂肪酸は、脂質の主要な基本骨格であり、脂質摂取の多寡により、様々な身体応答が惹起される。なかでも近年注目されているのが、高脂肪食ならびに長鎖脂肪酸摂取量により変化する脳内脂質恒常性(リポクオリティ)が、記憶・学習・情動などの脳機能以外にも、精神疾患をはじめとする様々な神経病態に関連する可能性である。本申請では、ニューロンとグリア細胞の機能的・構造的ネットワークに着目しながら、脂肪酸栄養によって変化する脳(神経系細胞)の脂質(リポ)クオリティを制御する分子基盤の解明と、その正常脳機能および精神疾患における病態生理学的意義を動物レベルで検証する。

Outline of Final Research Achievements

Although higher brain functions and neurological diseases have been linked to nutritional intake, the molecular basis of the effects of lipids on the nervous system has remained unclear. In this application, we examined whether changes in lipid metabolism in nervous system cells (neurons and glial cells) are related to the regulation of genetic information (epigenetic modification) and neural plasticity. The results revealed that changes in intracellular lipid metabolism and energy production affect the stress response of glial cells and the plasticity of neurons.

Academic Significance and Societal Importance of the Research Achievements

脂質の摂取障害が、学習や情動などに影響を及ぼすことは栄養学的に古くから知られているが、脂質摂取の異常(あるいは脂質代謝関連遺伝子変異)と神経可塑性異常の関連性の解析は重要なテーマである。本成果は、脳機能に対する発達期栄養学的知見、すなわち発達期栄養障害仮説を起点にした脳機能や神経系疾患病態の関連理解に向けて重要な知見を提供する。未だ謎の多い精神疾患病態メカニズムの解明に向けて、新たな基礎的知見と治療アプローチを提供できると考える。

Report

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

    (27 results)

All 2022 2021 2020 2019

All Journal Article (9 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 9 results,  Open Access: 8 results) Presentation (18 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] Environmental enrichment sex-dependently rescues memory impairment in FABP5 KO mice not mediated by brain-derived neurotrophic factor.2022

    • Author(s)
      Marion M, Hamilton J, Richardson B, Roeder N, Figueiredo A, Nubelo A, Hetelekides E, Penman S, Owada Y, Kagawa Y, Thanos PK.
    • Journal Title

      Behav Brain Res

      Volume: 425, Pages: 113814-113827

    • DOI

      10.1016/j.bbr.2022.113814

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Nuclear FABP7 regulates cell proliferation of wild-type IDH1 glioma through caveolae function.2022

    • Author(s)
      Kagawa Y, Umaru BA, Kanamori M, Zama R, Shil SK, Miyazaki H, Kobayashi S, Wannakul T, Yang S, Tominaga T, Owada Y.
    • Journal Title

      Mol Oncol

      Volume: 16 Issue: 1 Pages: 289-306

    • DOI

      10.1002/1878-0261.13130

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Suppression of α-synuclein propagation after intrastriatal injection in FABP3 null mice2021

    • Author(s)
      Matsuo Kazuya、Kawahata Ichiro、Melki Ronald、Bousset Luc、Owada Yuji、Fukunaga Kohji
    • Journal Title

      Brain Research

      Volume: 1760 Pages: 147383-147383

    • DOI

      10.1016/j.brainres.2021.147383

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Fatty acid‐binding protein 3 controls contact hypersensitivity through regulating skin dermal Vγ4 + γ/δ T cell in a murine model2020

    • Author(s)
      Kobayashi Shuhei、Phung Hai The、Kagawa Yoshiteru、Miyazaki Hirofumi、Takahashi Yu、Asao Atsuko、Maruyama Takashi、Yoshimura Akihiko、Ishii Naoto、Owada Yuji
    • Journal Title

      Allergy

      Volume: - Issue: 6 Pages: 1776-1788

    • DOI

      10.1111/all.14630

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Fatty acid binding protein 3 regulates differentiation of IgM-producing plasma cells.2020

    • Author(s)
      Shuhei Kobayashi, Hai The Phung, Shunichi Tayama, Yoshiteru Kagawa, Hirofumi Miyazaki, Yui Yamamoto, Takashi Maruyama, Naoto Ishii, Yuji Owada
    • Journal Title

      The FEBS Journal

      Volume: In Press Issue: 4 Pages: 1130-1141

    • DOI

      10.1111/febs.15460

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The fatty acid binding protein FABP7 is required for optimal oligodendrocyte differentiation during myelination but not during remyelination2020

    • Author(s)
      Foerster Sarah、Guzman de la Fuente Alerie、Kagawa Yoshiteru、Bartels Theresa、Owada Yuji、Franklin Robin J. M.
    • Journal Title

      Glia

      Volume: 68 Issue: 7 Pages: 1410-1420

    • DOI

      10.1002/glia.23789

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] “Passenger gene” problem in transgenic C57BL/6 mice used in hearing research2019

    • Author(s)
      Suzuki Jun、Inada Hitoshi、Han Chul、Kim Mi-Jung、Kimura Ryuichi、Takata Yusuke、Honkura Yohei、Owada Yuji、Kawase Tetsuaki、Katori Yukio、Someya Shinichi、Osumi Noriko
    • Journal Title

      Neuroscience Research

      Volume: - Pages: 30469-9

    • DOI

      10.1016/j.neures.2019.10.007

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The Role of Fatty Acid Binding Protein 7 in Spinal Cord Astrocytes in a Mouse Model of Experimental Autoimmune Encephalomyelitis2019

    • Author(s)
      Kamizato Kenyu、Sato Sho、Shil Subrata Kumar、Umaru Banlanjo A.、Kagawa Yoshiteru、Yamamoto Yui、Ogata Masaki、Yasumoto Yuki、Okuyama Yuko、Ishii Naoto、Owada Yuji、Miyazaki Hirofumi
    • Journal Title

      Neuroscience

      Volume: - Pages: 120-129

    • DOI

      10.1016/j.neuroscience.2019.03.050

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The guanylate cyclase C agonist linaclotide ameliorates the gut?cardio?renal axis in an adenine-induced mouse model of chronic kidney disease2019

    • Author(s)
      Nanto-Hara F、Kanemitsu Y、Fukuda S、Kikuchi K、Asaji K、Saigusa D、Iwasaki T、Ho H、Mishima E、Suzuki T、Suzuki C、Tsukimi T、Matsuhashi T、Oikawa Y、Akiyama Y、Kure S、Owada Y、Tomioka Y、Soga T、Ito S, Abe T
    • Journal Title

      Nephrology Dialysis Transplantation

      Volume: 35 Pages: 250-264

    • DOI

      10.1093/ndt/gfz126

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 核内FABP7はカベオラ機能調節を介してIDH1野生型グリオーマの増殖を制御する2022

    • Author(s)
      香川慶輝, Banlanjo Abdulaziz Umaru, 大和田祐二
    • Organizer
      第127回日本解剖学会全国学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 核内受容体PPARaに着目した統合失調症病態メカニズムの解明2022

    • Author(s)
      前川素子, 和田唯奈, 吉町文子, 大西哲生, 吉川武男, 大和田祐二
    • Organizer
      第127回日本解剖学会全国学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] FABP7-Oleic acid interaction potently drives glioma cell proliferation via nuclear lipid droplet formation and epigenetic regulation2022

    • Author(s)
      Banlanjo Abdulaziz Umaru, Yoshiteru Kagawa, Yuji Owada
    • Organizer
      第127回日本解剖学会全国学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 脂肪酸結合蛋白質 3 が内側前頭前野の発達に与える影響2022

    • Author(s)
      山本由似, 尾形雅君, 大和田祐二, 上条 桂樹
    • Organizer
      第127回日本解剖学会全国学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Effects of oleic acid on the amyloid‐β uptake in microglial cells2022

    • Author(s)
      Shuhan Yang, Hirofumi Miyazaki, Yuji Owada
    • Organizer
      第127回日本解剖学会全国学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Role of fatty acid-binding protein 3 on the development of the medial prefrontal cortex2022

    • Author(s)
      山本由似, 尾形雅君, 大和田祐二, 上条 桂樹
    • Organizer
      第95回日本薬理学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Fatty acid-binding protein 3 controls contact hypersensitivity through regulating skin dermal Vγ4+ γ/δ T cell development.2021

    • Author(s)
      Shuhei Kobayashi, Yoshiteru Kagawa, Hirofumi Miyazaki, Yuji Owada
    • Organizer
      第126回日本解剖学会全国学術集会・第98回日本生理学会大会合同大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Fatty acid-binding protein 7 modulates liver fibrosis by regulating the anti-inflammatory activation of liver macrophages2021

    • Author(s)
      Hirofumi Miyazaki, Shuhan Yang, Yuji Owada
    • Organizer
      第126回日本解剖学会全国学術集会・第98回日本生理学会大会合同大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] カルボニルストレスの亢進はヒトiPS細胞由来の神経細胞にミトコンドリア機能障害をもたらす:統合失調症の病態への関連性2021

    • Author(s)
      原 伯徳, 豊島 学, 久野 泰子, 大和田 祐二, 吉川 武男
    • Organizer
      第126回日本解剖学会全国学術集会・第98回日本生理学会大会合同大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Ndufs4 regulates synaptophysin expression in hippocampus2021

    • Author(s)
      Subrata Kumar Shil, Yoshiteru Kagawa, Banlanjo Abdulaziz Umaru, Takaaki Abe, Yuji Owada
    • Organizer
      第126回日本解剖学会全国学術集会・第98回日本生理学会大会合同大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Analysis of long chain fatty acid treatment on MG6 microglial cells2021

    • Author(s)
      Shuhan Yang, Hirofumi Miyazaki, Yuji Owada
    • Organizer
      第126回日本解剖学会全国学術集会・第98回日本生理学会大会合同大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 悪性グリオーマでIDH遺伝子変異の有無とFABP7の発現・核局在は相関する2020

    • Author(s)
      香川慶輝, Umaru Banlanjo Abdulaziz, 大和田祐二
    • Organizer
      第125回日本解剖学会学術総会全国学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] FABP7は細胞内脂質代謝制御を介してマクロファージの抗炎症性機能に関わる2020

    • Author(s)
      宮崎啓史, 香川慶輝, 小林周平, 大和田祐二
    • Organizer
      第125回日本解剖学会学術総会全国学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 脂肪酸結合タンパク質3(FABP3)が前帯状皮質におけるパルブアルブミン発現とペリニューロナルネット形成に及ぼす影響2020

    • Author(s)
      山本由似, 尾形雅君, 上条桂樹, 大和田祐二
    • Organizer
      第125回日本解剖学会学術総会全国学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] FABP7によるacetyl-CoA代謝の制御機構2019

    • Author(s)
      香川慶輝, Banlanjo Abdulaziz Umaru, 大和田祐二
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] The mechanism of epigenetic regulation by nuclear fatty acid binding protein 7 (FABP7)2019

    • Author(s)
      Yoshiteru Kagawa, Banlanjo A Umaru, Yuji Owada
    • Organizer
      60th International Conference on the Bioscience of Lipids
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Fatty acid binding protein 3 (FABP3) in the anterior cingulate cortex modulates the methylation status of the glutamic decarboxylase67 promoter region2019

    • Author(s)
      Yui Yamamoto, Yuji Owada
    • Organizer
      60th International Conference on the Bioscience of Lipids
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The involvement of fatty acid binding protein 5 in the blood-brain barrier transport of docosahexaenoic acid and cognition2019

    • Author(s)
      Yijun Pan, Joseph Nicolazzo, Yuji Owada
    • Organizer
      60th International Conference on the Bioscience of Lipids
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research

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

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