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Significance of lipid metabolism in glial cell function: association with psychiatiric diseases

Research Project

Project/Area Number 16H05116
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General anatomy (including histology/embryology)
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)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2018: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2016: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000)
Keywordsグリア細胞 / 遺伝子欠損マウス / エピゲノム / 長鎖脂肪酸 / GABA / アストロサイト / 脱髄モデル / オリゴデンドロサイト前駆細胞 / ノックアウトマウス / 脂肪酸結合蛋白質 / 視床下部 / 脂質 / リポカイン / 遺伝子ノックアウトマウス / 脂肪酸結合タンパク質 / グリア / 睡眠 / オリゴデンドロサイト / 脂肪酸
Outline of Final Research Achievements

In this study, we aimed to clarify the molecular basis how the cellular lipid environment affects the function of neural cells including neurons and glia. In addition, we also explored whether alteration of brain lipid metabolism is associated with the normal or pathological brain functions. We mainly revealed that fatty acid binding protein (FABP) in the cortical neurons is involved in the expression of behaviors through its epigenetic regulation of neurotransmitter synthesis, and that FABP in glia is important in the control of glial lipid metabolism and it is also involved in the glial proliferation and neuronal plasticity control through epigenetic regulation of lipid metabolism.
These results are expected to contribute to research and development in the fields of psychiatry and health sciences.

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。しかしながら、脂質摂取の異常(あるいは脂質代謝関連分子の異常)と神経活動の関連性については、未だ不明な点が多い。本研究成果は、脳機能を正常に保つには、神経系細胞において脂質を適切に調節・維持することが重要であることを示している。言い換えれば、その調節が上手くいかない場合には、精神疾患をはじめとする脳疾患につながることを意味している。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (34 results)

All 2019 2018 2017 2016 2015

All Journal Article (14 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 14 results,  Open Access: 10 results,  Acknowledgement Compliant: 1 results) Presentation (20 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] FABP7 Protects Astrocytes Against ROS Toxicity via Lipid Droplet Formation2019

    • Author(s)
      Islam Ariful、Kagawa Yoshiteru、Miyazaki Hirofumi、Shil Subrata Kumar、Umaru Banlanjo A.、Yasumoto Yuki、Yamamoto Yui、Owada Yuji
    • Journal Title

      Molecular Neurobiology

      Volume: - Issue: 8 Pages: 5763-5779

    • DOI

      10.1007/s12035-019-1489-2

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of FABP7 in tumor cell signaling2019

    • Author(s)
      Kagawa Yoshiteru、Umaru Banlanjo A.、Ariful Islam、Shil Subrata Kumar、Miyazaki Hirofumi、Yamamoto Yui、Ogata Masaki、Owada Yuji
    • Journal Title

      Advances in Biological Regulation

      Volume: 71 Pages: 206-218

    • DOI

      10.1016/j.jbior.2018.09.006

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fatty acid binding protein 7 may be a marker and therapeutic targets in clear cell renal cell carcinoma2018

    • Author(s)
      Nagao Kazuhiro、Shinohara Nachi、Smit Frank、de Weijert Mirjam、Jannink Sander、Owada Yuji、Mulders Peter、Oosterwijk Egbert、Matsuyama Hideyasu
    • Journal Title

      BMC Cancer

      Volume: 18 Issue: 1 Pages: 1114-1114

    • DOI

      10.1186/s12885-018-5060-8

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] FABP3 in the Anterior Cingulate Cortex Modulates the Methylation Status of the Glutamic Acid Decarboxylase67 Promoter Region2018

    • Author(s)
      Yamamoto Yui、Kida Hiroyuki、Kagawa Yoshiteru、Yasumoto Yuki、Miyazaki Hirofumi、Islam Ariful、Ogata Masaki、Yanagawa Yuchio、Mitsushima Dai、Fukunaga Kohji、Owada Yuji
    • Journal Title

      The Journal of Neuroscience

      Volume: 38 Issue: 49 Pages: 10411-10423

    • DOI

      10.1523/jneurosci.1285-18.2018

    • NAID

      130007813353

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Down-regulation of fatty acid binding protein 7 (Fabp7) is a hallmark of the postpartum brain2018

    • Author(s)
      Driessen Terri M.、Zhao Changjiu、Saenz Marissa、Stevenson Sharon A.、Owada Yuji、Gammie Stephen C.
    • Journal Title

      Journal of Chemical Neuroanatomy

      Volume: 92 Pages: 92-101

    • DOI

      10.1016/j.jchemneu.2018.07.003

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Glial Fatty Acid-Binding Protein 7 (FABP7) Regulates Neuronal Leptin Sensitivity in the Hypothalamic Arcuate Nucleus2018

    • Author(s)
      Yasumoto Yuki、Miyazaki Hirofumi、Ogata Masaki、Kagawa Yoshiteru、Yamamoto Yui、Islam Ariful、Yamada Tetsuya、Katagiri Hideki、Owada Yuji
    • Journal Title

      Molecular Neurobiology

      Volume: - Issue: 12 Pages: 9016-9028

    • DOI

      10.1007/s12035-018-1033-9

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Origin and development of septoclasts in endochondral ossification of mice.2018

    • Author(s)
      Bando Y, Sakashita H, Taira F, Miyake G, Ogasawara Y, Sakiyama K, Owada Y, Amano O
    • Journal Title

      Hsitochem. Cell Biol.

      Volume: 印刷中 Issue: 6 Pages: 645-654

    • DOI

      10.1007/s00418-018-1653-1

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ramelteon improves post-traumatic stress disorder-like behaviors exhibited by fatty acid binding protein 3 null mice2018

    • Author(s)
      Yabuki Y, Takahata I, Matsuo K, Owada Y, Fukunaga K
    • Journal Title

      Mol Neurobiol

      Volume: 55 Pages: 3577-3591

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Infection Programs Sustained Lymphoid Stromal Cell Responses and Shapes Lymph Node Remodeling upon Secondary Challenge.2017

    • Author(s)
      Gregory JL, Walter A, Alexandre YO, Hor JL, Liu R, Ma JZ, Devi S, Tokuda N, Owada Y, Mackay LK, Smyth GK, Heath WR, Mueller SN.
    • Journal Title

      Cell Rep

      Volume: 18 Issue: 2 Pages: 406-418

    • DOI

      10.1016/j.celrep.2016.12.038

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Microglia-derived neuregulin expression in psychiatric disorders.2017

    • Author(s)
      Ikawa D, Makinodan M, Iwata K, Ohgidani M, Kato TA, Yamashita Y, Yamamuro K, Kimoto S, Toritsuka M, Yamauchi T, Fukami SI, Yoshino H, Okumura K, Tanaka T, Wanaka A, Owada Y, Tsujii M, Sugiyama T, Tsuchiya K, Mori N, Hashimoto R, Matsuzaki H, Kanba S, Kishimoto T.
    • Journal Title

      Brain Behav Immun.

      Volume: 61 Pages: 375-385

    • DOI

      10.1016/j.bbi.2017.01.003

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Motor training promotes both synaptic and intrinsic plasticity of layer II/III pyramidal neurons in the primary motor cortex.2016

    • Author(s)
      Kida H, Tsuda Y, Ito N, Yamamoto Y, Owada Y, Kamiya Y, Mitsushima D.
    • Journal Title

      Cerebral Cortex

      Volume: in press Issue: 8 Pages: 3494-507

    • DOI

      10.1093/cercor/bhw134

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Characterization of Fatty Acid Binding Protein 7 (FABP7) in the Murine Retina.2016

    • Author(s)
      Su X, Tan QS, Parikh BH, Tan A, Mehta MN, Sia Wey Y, Tun SB, Li LJ, Han XY, Wong TY, Hunziker W, Luu CD, Owada Y, Barathi VA, Zhang SS, Chaurasia SS.
    • Journal Title

      Invest Ophthalmol Vis Sci

      Volume: 57 Issue: 7 Pages: 3397-408

    • DOI

      10.1167/iovs.15-18542

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Fatty Acid-Binding Protein 5 at the Blood-Brain Barrier Regulates Endogenous Brain Docosahexaenoic Acid Levels and Cognitive Function.2016

    • Author(s)
      Pan Y, Short JL, Choy KH, Zeng AX, Marriott PJ, Owada Y, Scanlon MJ, Porter CJ, Nicolazzo JA.
    • Journal Title

      J Neurosci.

      Volume: 36 Issue: 46 Pages: 11755-11767

    • DOI

      10.1523/jneurosci.1583-16.2016

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Immunohistochemical analysis of sustentacular cells in the adrenal medulla, carotid body and sympathetic ganglion of mice using an antibody against brain-type fatty acid binding protein (B-FABP).2015

    • Author(s)
      Pakkarato S, Chomphoo S, Kagawa Y, Owada Y, Mothong W, Iamsaard S, Sawatpanich T, Kondo H, Hipkaeo W.
    • Journal Title

      J Anat

      Volume: 226 Issue: 4 Pages: 348-353

    • DOI

      10.1111/joa.12285

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 細胞核内FABP7とATP citrate lyase (ACLY) の相互作用によるエピゲノム制御機構2018

    • Author(s)
      香川慶輝, 大和田祐二
    • Organizer
      第41回日本分子生物学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Role of FABP7 in astrocytes and its possibe association with psychiatric diseases.2018

    • Author(s)
      Yuji Owada
    • Organizer
      59th International Symposium on "Biological Regulation and Enzyme Activity in Normal and Neoplastic Tissues
    • Related Report
      2018 Annual Research Report
  • [Presentation] 脂肪酸結合タンパク質によるエピゲノム制御2018

    • Author(s)
      大和田祐二
    • Organizer
      第91回日本生化学会大会シンポジウム「脂肪酸シグナリングに関与するFABP研究の新展開」
    • Related Report
      2018 Annual Research Report
  • [Presentation] 脂肪酸結合タンパク質(FABP)を通して精神疾患を理解する2018

    • Author(s)
      大和田祐二
    • Organizer
      第14回REDEEMシンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] アストロサイトにおける脂肪酸結合蛋白質FABP7の機能解析.2018

    • Author(s)
      香川慶輝, 大和田祐二
    • Organizer
      第123回日本解剖学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ミトコンドリア呼吸鎖複合体I構成蛋白質Ndufs4がアストロサイトのミトコンドリア機能におよぼす役割2018

    • Author(s)
      南都文香, Angelina Misiou, Subrata Kumar Shil, 阿部高明, 大和田祐二
    • Organizer
      第123回日本解剖学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 脂肪酸結合蛋白質FABP3による介在ニューロンのエピゲノム調節機構2018

    • Author(s)
      山本由似, 木田裕之, 美津島大, 福永浩司, 尾形雅君, 上条桂樹, 大和田祐二
    • Organizer
      第123回日本解剖学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] FABP7 protects astrocyte against ROS toxicity under ROS stress2018

    • Author(s)
      Ariful Islam, Yoshiteru Kagawa, Hirofumi Miyazaki, Subrata Kumar Shil, Yuji Owada
    • Organizer
      第123回日本解剖学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] FABP7は核内Acetyl-CoAレベル調節を介してエピジェネティックに遺伝子発現を制御する2018

    • Author(s)
      香川慶輝, 大和田祐二
    • Organizer
      第40回日本分子生物学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] FABP3はGAD67のプロモーター領域のメチル化状態を制御することで認知、情動行動に関与する2017

    • Author(s)
      山本由似, 木田裕之, 美津島大, 澤田知夫, 福永浩司, 石田雄介, 上条桂樹, 大和田祐二
    • Organizer
      第122回 日本解剖学会総会
    • Place of Presentation
      長崎市 長崎大学
    • Year and Date
      2017-03-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] FABP7は視床下部アストロサイトにおけるレプチン感受性を調節し、高脂肪食摂取量を抑制する2017

    • Author(s)
      安本有希, 宮崎啓史, 大和田祐二
    • Organizer
      第122回 日本解剖学会総会
    • Place of Presentation
      長崎市 長崎大学
    • Year and Date
      2017-03-29
    • Related Report
      2016 Annual Research Report
  • [Presentation] 腸上皮細胞間リンパ球(IEL)の抗体刺激に伴う絨毛上皮細胞の剥離機構2017

    • Author(s)
      尾形雅君, 香川慶輝, 安本有希, 伊藤恒敏, 大和田祐二
    • Organizer
      第122回 日本解剖学会総会
    • Place of Presentation
      長崎市 長崎大学
    • Year and Date
      2017-03-29
    • Related Report
      2016 Annual Research Report
  • [Presentation] FABPによって制御される細胞内代謝がマクロファージ機能に及ぼす影響2017

    • Author(s)
      宮崎啓史, 大和田祐二
    • Organizer
      第122回 日本解剖学会総会
    • Place of Presentation
      長崎市 長崎大学
    • Year and Date
      2017-03-28
    • Related Report
      2016 Annual Research Report
  • [Presentation] 脂肪酸結合蛋白質3(FABP3)は前帯状皮質においてGAD67プロモーターのメチル化を制御する2017

    • Author(s)
      山本由似, 木田裕之, 美津島大, 大和田祐二, 福永浩司
    • Organizer
      第90回 日本薬理学会年会
    • Place of Presentation
      長崎市 ブルックホール
    • Year and Date
      2017-03-16
    • Related Report
      2016 Annual Research Report
  • [Presentation] 核内FABP7はエピジェネティックなcaveolin-1の発現制御に関与する2016

    • Author(s)
      香川慶輝, Ariful Islam, 尾形雅君, 大和田祐二
    • Organizer
      第39回 日本分子生物学会年会
    • Place of Presentation
      横浜市 パシフィコ横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] 前帯状皮質のGABAシステム制御機構における脂肪酸結合タンパク質の役割2016

    • Author(s)
      山本由似, 福永浩司, 大和田祐二
    • Organizer
      第38回 日本生物学的精神医学会
    • Place of Presentation
      福岡市 福岡国際会議場
    • Year and Date
      2016-09-09
    • Related Report
      2016 Annual Research Report
  • [Presentation] 脂肪酸結合蛋白質FABP7の細胞核局在の意義ーcaveolin-1遺伝子発現制御との関連ー2016

    • Author(s)
      香川慶輝, Ariful Islam, 尾形雅君, 大和田祐二
    • Organizer
      第62回 日本解剖学会 東北・北海道連合支部学術集会
    • Place of Presentation
      帯広市 帯広畜産大学
    • Year and Date
      2016-09-03
    • Related Report
      2016 Annual Research Report
  • [Presentation] 脂肪酸結合蛋白質は前帯状皮質のGABAシステムを制御する2016

    • Author(s)
      山本由似, 石田雄介, 上条桂樹, 大和田祐二
    • Organizer
      第62回 日本解剖学会 東北・北海道連合支部学術集会
    • Place of Presentation
      帯広市 帯広畜産大学
    • Year and Date
      2016-09-03
    • Related Report
      2016 Annual Research Report
  • [Presentation] 視床下部グリアに発現するFABP7のレプチン感受性と摂食行動における機能2016

    • Author(s)
      安本有希, 大和田祐二
    • Organizer
      第62回 日本解剖学会 東北・北海道連合支部学術集会
    • Place of Presentation
      帯広市 帯広畜産大学
    • Year and Date
      2016-09-03
    • Related Report
      2016 Annual Research Report
  • [Presentation] Possible role of hypothalamic FABP7 in the cotrol of glial cell proliferation and leptin sensitivity2016

    • Author(s)
      Yasumoto Y and Owada Y
    • Organizer
      Cold Spring Harbor Laboratory Meeting - Glia in Health and Disease
    • Place of Presentation
      Cold Spring Harbor Laboratoy, NY, USA
    • Year and Date
      2016-07-26
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research

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Published: 2016-04-21   Modified: 2020-03-30  

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