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Development of GPR40-positive neural stem cells for the brain restoration

Research Project

Project/Area Number 22390273
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionKanazawa University

Principal Investigator

YAMASHIMA Tetsumori  金沢大学, 医学系, 准教授 (60135077)

Project Period (FY) 2010-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
Fiscal Year 2013: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2012: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2011: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2010: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Keywordsサル / 海馬 / 骨髄幹細胞 / GPR40 / 多価不飽和脂肪酸 / ドコサヘキサエン酸 / ニューロン新生 / 脳再生療法 / CA-2,3 / CREB / BDNF / 苔状線維 / シナプス / CREB / BDNF / TrkB / 骨髄間葉系幹細胞 / bFGF / receptor internalization
Research Abstract

Vascular adventitia is a potential source of neuronal stem/progenitor cells in the neurogenic niche of adult monkey hippocampus, and the fatty acid receptor GPR40 is expressed here. As perivascular progenitors might be regarded as in situ counterparts of bone marrow stroma, we studied outcome of clonally-expanded bone marrow-derived multipotent mesenchymal stromal cells (BM-MSC) in response to DHA. During expansion the cell population was enriched in GPR40. DHA in addition to bFGF yielded a mature neuronal phenotype acquisition with a significant GPR40 up-regulation two weeks after culture. Compared to bFGF alone, there were not only quantitative but also temporally-relevant induction of neuronal specific transcripts and proteins. Along with the morphological changes and phenotype acquisition, DHA-dependent GPR40 up-regulation showed a cell cycle arrest implying ongoing differentiation. These data suggest that a DHA/GPR40-mediated mechanism may be involved in the adult neurogenesis.

Report

(5 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (23 results)

All 2013 2012 2011 2010 Other

All Journal Article (10 results) (of which Peer Reviewed: 10 results) Presentation (7 results) (of which Invited: 1 results) Book (4 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Reconsider Alzheimer's disease by the 'calpain-cathepsin hypothesis' -A perspective review2013

    • Author(s)
      Yamashima T
    • Journal Title

      Progress in Neurobiology

      Volume: 105 Pages: 1-23

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Reconsider Alzheimer’s disease by the ‘calpain-cathepsin hypothesis’ ―A perspective review2013

    • Author(s)
      Tetsumori Yamashima
    • Journal Title

      Progress in Neurobiology

      Volume: 105 Pages: 1-23

    • DOI

      10.1016/j.pneurobio.2013.02.004

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] New insights into "GPR40-CREB interaction inadult neurogenesis" specific for primates2012

    • Author(s)
      Boneva NB, Yamashima T
    • Journal Title

      Hippocampus

      Volume: 22(4) Issue: 4 Pages: 896-905

    • DOI

      10.1002/hipo.20951

    • Related Report
      2012 Annual Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Why are hippocampal CA1 neurons vulnerable but motor cortex neurons resistant to transient ischemia?2012

    • Author(s)
      Zhu H, Yoshimoto T, Imajo-Ohmi S, Dazortsava M, Mathivanan A, Yamashima T.
    • Journal Title

      J Neurochem.

      Volume: 120 Issue: 4 Pages: 575-585

    • DOI

      10.1111/j.1471-4159.2011.07550.x

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 'PUFA-GPR40-CREB signaling' hypothesis for the adult primate neurogenesis.2012

    • Author(s)
      Yamashima T.
    • Journal Title

      Prog Lipid Res.

      Volume: 51 Issue: 3 Pages: 221-231

    • DOI

      10.1016/j.plipres.2012.02.001

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of fatty acid-binding proteins in adult hippocampal neurogenic niche of postischemic monkeys2011

    • Author(s)
      Boneva NB, Kaplamadzhiev DB, Sahara S, Kikuchi H, Pyko IV, Kikuchi M, Tonchev AB, Yamashima T
    • Journal Title

      Hippocampus

      Volume: 21(2) Issue: 2 Pages: 162-171

    • DOI

      10.1002/hipo.20732

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neuroprotective and Ameliorative Actions of Polyunsaturated Fatty Acids Against Neuronal Diseases:Implication of Fatty Acid-Binding Proteins (FABP) and G Protein-Coupled Receptor 40 (GPR40) in Adult Neurogenesis2011

    • Author(s)
      Boneva NB, Kikuchi M, Minabe Y, Yamashima T
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 116 Issue: 2 Pages: 163-172

    • DOI

      10.1254/jphs.10R34FM

    • NAID

      10029894501

    • ISSN
      1347-8613, 1347-8648
    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Differential expression of FABP 3, 5, 7 in infantile and adult monkey cerebellum2010

    • Author(s)
      Boneva NB, 他7名
    • Journal Title

      Neurosci Res

      Volume: 68 Pages: 94-102

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bone marrow-derived stromal cells can express neuronal markers by DHA/GPR40 signaling2010

    • Author(s)
      Kaplamadzhiev DB, 他11名
    • Journal Title

      Biosci Trends

      Volume: 4 Pages: 119-129

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] DHA promotes the neuronal differentiation of rat neural stem cells transfected with GPR40 gene2010

    • Author(s)
      Ma D, 他7名
    • Journal Title

      Brain Res

      Volume: 1330 Pages: 1-8

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] 虚血性と変性性の神経細胞死2013

    • Author(s)
      山嶋 哲盛
    • Organizer
      第22回海馬と高次脳機能学会
    • Place of Presentation
      金沢
    • Year and Date
      2013-10-12
    • Related Report
      2013 Final Research Report
  • [Presentation] Reconsider アルツハイマー病2012

    • Author(s)
      山嶋 哲盛
    • Organizer
      第21回海馬と高次脳機能学会
    • Place of Presentation
      金沢・湯涌創作の森
    • Related Report
      2012 Annual Research Report
  • [Presentation] Adult neurogenesis specific for primates2011

    • Author(s)
      Tetsumori YAMASHIMA
    • Organizer
      8^<th> World Congress of IBRO
    • Place of Presentation
      パッソ要塞会議場(イタリア)
    • Year and Date
      2011-07-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] Birth and death of hippocampal neurons after cerebral ischemia in adult primates2010

    • Author(s)
      Yamashima Tetsumori
    • Organizer
      5^<th> International Conference of Neurosurgery Shanghai
    • Place of Presentation
      Shanghai International Convention Center, Shanghai, China
    • Year and Date
      2010-11-19
    • Related Report
      2010 Annual Research Report
  • [Presentation] 虚血性と変性性の神経細胞死

    • Author(s)
      山嶋哲盛
    • Organizer
      第22回海馬と高次脳機能学会
    • Place of Presentation
      金沢
    • Related Report
      2013 Annual Research Report
  • [Presentation] Reconsider Alzheimer's disease by the calpain-cathepsin hypothesis

    • Author(s)
      Tetsumori Yamashima
    • Organizer
      AAIC 2013(国際アルツハイマー学会)
    • Place of Presentation
      アメリカ/ボストン
    • Related Report
      2013 Annual Research Report
  • [Presentation] Why are hippocampal neurons vulnerable to transient cerebral ischemia ?

    • Author(s)
      Tetsumori Yamashima
    • Organizer
      FASEB seminar
    • Place of Presentation
      アメリカ/ベローフォール
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Book] サラダ油が脳を殺す-「錆び」から身体を守る2012

    • Author(s)
      山嶋 哲盛
    • Total Pages
      218
    • Publisher
      河出書房新社
    • Related Report
      2013 Final Research Report
  • [Book] サラダ油が脳を殺す2012

    • Author(s)
      山嶋 哲盛
    • Total Pages
      239
    • Publisher
      河出書房新社
    • Related Report
      2012 Annual Research Report
  • [Book] Neurogenesis in the adult brain II Clinical implications (Seki T. et al., eds)2011

    • Author(s)
      Tetsumori YAMASHIMA
    • Total Pages
      211
    • Publisher
      Springer
    • Related Report
      2011 Annual Research Report
  • [Book] Acute Neuronal Injury2010

    • Author(s)
      Anton Tonchev, Tetsumori Yamashima
    • Total Pages
      306
    • Publisher
      Springer
    • Related Report
      2010 Annual Research Report
  • [Patent(Industrial Property Rights)] GPR40陽性骨髄幹細胞2011

    • Inventor(s)
      山嶋哲盛
    • Industrial Property Rights Holder
      金沢大学
    • Industrial Property Number
      2010-000736
    • Filing Date
      2011-01-05
    • Related Report
      2010 Annual Research Report
  • [Patent(Industrial Property Rights)] GPR40陽性骨髄幹細胞2010

    • Inventor(s)
      山嶋 哲盛
    • Industrial Property Rights Holder
      金沢大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2011-548981
    • Filing Date
      2010-12-28
    • Related Report
      2013 Final Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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