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Study on the molecular mechanism by which microglia transform into phagocytes

Research Project

Project/Area Number 15500269
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionSoka University

Principal Investigator

NAKAJIMA Kazuyuki  Soka University, Dept.of Bioinformatics, Associate prof., 工学部, 助教授 (50175494)

Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2005: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
KeywordsMicrogila / Macrophages / Phagocytes / Neuronal cell death / Neurobiology / 貪食 / 細胞死 / 顔面神経 / 貧食細胞
Research Abstract

Little has been known about the mechanism by which resting microglia change into active phagocytes. Therefore, I aimed to identify the specific molecule(s) associated with the induction of phagocytic activity in activated microglia.
In the first year, we tried to establish an animal model of neuronal cell death induced by the injection of neurotoxic lectin RCA6O into facial nerve. However, the experiment was not carried out because RCA60 was not available in Japan. Instead, we used hydrogen peroxide or peroxinitrite to induce neuronal cell death. These radicals were found to be effective for injuring motoneurons in facial nucleus.
In the second year, the molecules associated with the induction of phagocytic activity were explored by subtraction method in the hydrogen peroxide-injected facial nucleus. The subtraction method revealed that some molecules are induced in hydrogen peroxide-injected facial nucleus, but the most of the molecules belongs to proteases, other enzymes and cytoskelet … More ons. Despite the repeated experiments, we could not find out candidate molecules for phagocytic activity-related proteins. Apart from the in vivo model, we tried to prepare non-phagocytic microglia in vitro, and finally succeeded to do it by treating microglia with phorbol myristate acetate (PMA). Thus, it became possible to compare the proteins between phagocytic microglia and non-phagocytic microglia.
In the last year, we continued to analyze the phagocytes-related proteins by subtraction method. However, the results were not significant. On the other hand, the comparison of proteins between phagocytic microglia and non-phagocytic microglia indicated that a molecule with molecular weight of approximately 90 kDa and pl 4.8 is present in phagocytic microglia. Therefore, the molecule (p90) was tried to be isolated from the cultured microglia. The microglial homogenate was applied to DEAE Sephadex, Hydroxyapatite, Sephacryl S200 column chromatographies, and subsequently SDS polyacrylamide gel electrophoresis/transblotting. Finally, p90 on PVDF membrane was analyzed for N-terminal amino acid sequence. The resultant sequence was Asp-Asp-Glu-Val-----(not opened). These results including the identification and the amino acid sequence of p90 remain to be confirmed. Less

Report

(4 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (21 results)

All 2006 2005 2004 Other

All Journal Article (17 results) Book (1 results) Publications (3 results)

  • [Journal Article] Nonparticipation of nuclear factor kappa B (NFκB) in the signaling cascade of c-Jun N-terminal kinase (JNK)- and p38 mitogen-activated protein kinase (p38MAPK)-dependent tumor necrosis factor alpha (TNFα)induction in lipopolysaccharide (LPS)-simulated microglia.2006

    • Author(s)
      Uesugi M
    • Journal Title

      Brain Res. 1073-1074

      Pages: 48-59

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Nonparticipation of nuclear factor kappa B (NFκB) in the signaling cascade of c-Jun N-terminal kinase (JNK)-and p38 mitogen-activated protein kinase (p38MAPK)-dependent tumor necrosis factor alpha (TNFα) induction in lipopolysaccharide(LPS)-stimulated microglia2006

    • Author(s)
      Uesugi M
    • Journal Title

      Brain Res. 1073-1074

      Pages: 48-59

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Nonparticipation of nuclear factor kappa B (NFκB) in the signaling cascade of c-Jun N-terminal kinase (JNK)- and p38 mitogen-activated protein kinase (p38MAPK)-dependent tumor necrosis factor alpha (TNFα) induction in lipopolysaccharide (LPS)-stimulated microglia.2006

    • Author(s)
      Uesugi M
    • Journal Title

      Brain Res. 1073-1074

      Pages: 48-59

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Axotomy-dependent urokinase induction in the rat facial nucleus : possible stimulation of microglia by neurons.2005

    • Author(s)
      Nakajima K
    • Journal Title

      Neurochem. Int. 46

      Pages: 107-116

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Enhancement of urokinase-type plasminogen activator (uPA) secretion, but not that of substrate plasminogen (PGn), by rat microglis stimulated with neuronal conditioned medium.2005

    • Author(s)
      Nakajima K
    • Journal Title

      Neurosci Lett. 378

      Pages: 13-17

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Axotomy-dependent urokinase induction in the rat facial nucleus : possible stimulation of microglia by neurons2005

    • Author(s)
      Nakajima K
    • Journal Title

      Neurochem.Int. 46

      Pages: 107-116

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Enhancement of urokinase-type plasminogen activator(uPA) secretion, but not that of substrate plasminogen(PGn), by rat microglia stimulated with neuronal conditioned medium2005

    • Author(s)
      Nakajima K
    • Journal Title

      Neurosci Lett. 378

      Pages: 13-17

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Axotomy-dependent urokinase induction in the rat facial nucleus : possible stimulation of microglia by neurons.2005

    • Author(s)
      Nakajima K
    • Journal Title

      Neurochem.Int. 46

      Pages: 107-116

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Enhancement of urokinase-type plasminogen activator (uPA) secretion, but not that of substrate plasminogen (PGn), by rat microglia stimulated with neuronal conditioned medium.2005

    • Author(s)
      Nakajima K
    • Journal Title

      Neurosci Lett. 378

      Pages: 13-17

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Axotomy-dependent urokinase induction in the rat facial nucleus : possible stimulation of microglia by neurons2004

    • Author(s)
      Nakajima K et al.
    • Journal Title

      Neurochem Int. 45

      Pages: 107-116

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Microglia : Neuroprotective and neurotrophic cells in the central nervous system2004

    • Author(s)
      Nakajima K, Kohsaka S
    • Journal Title

      Current Drugs-Cardiovascular & Haematological Disorders 4

      Pages: 65-84

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Differential suppression of endotoxin-inducible inflammatory cytokines by nuclear factor kappa B (NFκB) inhibitor in rat microglia

    • Author(s)
      Nakajima K
    • Journal Title

      Neurosci. Lett. (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] In vitro proliferation of axotomized rat facial nucleus-derived activated microglia in an autocrine fashion

    • Author(s)
      Nakajima K
    • Journal Title

      J. Neurosci. Res. (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Differential suppression of endotoxin-inducible inflammatory cytokines by nuclear factor kappa B(NFκB) inhibitor in rat microglia

    • Author(s)
      Nakajima K
    • Journal Title

      Neurosci.Lett. in press

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] In vitro proliferation of axotomized rat facial nucleus-derived activated microglia in an autocrine fashion

    • Author(s)
      Nakajima K
    • Journal Title

      J.Neurosci.Res. in press

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Differential suppression of endotoxin-inducible inflammatory cytokines by nuclear factor kappa B (NFκB) inhibitor in rat microglia

    • Author(s)
      Nakajima K
    • Journal Title

      Neurosci.Lett. (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] In vitro proliferation of axotomized rat facial nucleus-derived activated microglia in an autocrine fashion

    • Author(s)
      Nakajima K
    • Journal Title

      J.Neurosci.Res. (in press)

    • Related Report
      2005 Annual Research Report
  • [Book] Neuroglia second edition2005

    • Author(s)
      Nakajima K その他(共著)
    • Total Pages
      11
    • Publisher
      Oxford University Press
    • Related Report
      2004 Annual Research Report
  • [Publications] Nakajima K: "Activation of microglia with lipopolysaccharide leads to the prolonged decrease of conventional protein kinase C activity"Mol.Brain Res.. 110・1. 92-99 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nakajima K: "Suppression of lipopolysaccharide-dependent tumor necrosis factor α (TNFα) induction in rat microglia in which protein kinase Cα (PKCα) is downregulated"Neurosci.Lett.. 343・1. 33-36 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nakajima K: "Molecular mechanisms determining opposed functional states of microglia"Current Neuropharmacology. 4・1. 245-265 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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