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PURIFICATION AND CHARACTERZATION OF GLIA-DERIVED NEUROPROTECTIVE FACTORS

Research Project

Project/Area Number 10680745
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neuroscience in general
Research InstitutionEHIME UNIVERSITY

Principal Investigator

TANAKA Junya  MEDICINE, EHIME UNIV, PROFESSOR, 医学部, 教授 (70217040)

Co-Investigator(Kenkyū-buntansha) SUZUKI Youji  MEDICINE, EHIME UNIV, INSTRUCTOR, 医学部, 助手 (20226567)
MAEDA Nobuji  MEDICINE, EHIME UNIV, PROFESSOR, 医学部, 教授 (50036464)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥2,400,000 (Direct Cost: ¥2,400,000)
KeywordsMICROGLIA / ASTROCYTES / NEURON / APOPTOSIS / INHIBITION OF CELL DEATH
Research Abstract

We have found the followings regarding the neuroprotective effects in this project.
1) Neuroprotective effects of microglial cells. We found that cerebrocortical primary neurons died by apoptosis by incubating cells with sodium nitroprusside (SNP), a nitric oxide (NO)-donor compound, By the use of this apoptosis model, we investigated the effect of microglial cells on neuronal survival. As a result, the NO-induced neuronal apoptosis was completely prevented by microglial cells that were cocultured with neurons. Since the neuronal apoptosis was also largely inhibited by microglial conditioned medium, microglia-derived anti-apoptotic factor may be a soluble-factor(s). Furthermore, the conditioned medium was effective when it was applied after exposure to NO. Among a variety of known cytokines and growth factors that are produced by microglial cells, only tumor necrosis factor a significantly rescued neurons against NO-induced damage. 2) Neuroprotective effects of astrocytes. We investigated to determine whether astrocytes could rescue primary cerebrocortical neurons from reactive oxygen species (ROS)-induced apoptosis. By adding SNP, 3-morpholinosydononimine (SIN-1) or mixture of FeSO4 and ascorbic acid, NO, superoxide anion or hydroxyl radicals were introduced into culture plates of neurons. When astrocytes were cocultured with neurons, ROS-induced neuronal death was completely prevented. However, meningeal fibroblasts could not rescue neurons. When neurons were cultured on astrocytes-derived extracellular matrix (ECM), neuronal apoptosis was mostly prevented. The astrocyte-derived ECM contained laminin and fibronectin, and purified laminin and fibronectin significantly protected neurons against oxidative stress.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Igase K,Tanaka J,et al.: "An 18-mer peptide fragment of prosaposin ameliorates place navigation..."Journal of Cerebral Blood Flow and Metabolism. 19. 298-306 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tanaka J,Toku K et al.: "Morphological differentiation of microglial cells in culture : Involvement..."Neuroscience Research. 34. 207-215 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tanaka J,Toku K et al.: "Astrocytes prevent neuronal death induced by reactive oxygen and nitrogen..."Glia. 28. 85-96 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Toku K,Tanaka J,et al.: "Microglial cells prevent nitric oxide-induced neuronal apoptosis in vitro"Journal of Neuroscience Research. 53. 415-425 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakatuka H,Ohta S,Tanaka J,et al.: "Release of cytochrome c from mitochondria to cytosol in gerbil hippocampal..."Brain Research. 849. 216-219 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakatuka H,Ohta S,Tanala J,et al.: "Cytochrome c release from mitochondria to the cytosol was suppressed in..."Neuroscience Letters. 278. 53-56 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Keiji Igase. Junya Tanaka, Yoshiaki Kumon, Bo Zhang, Yasutaka Sadamoto, Nobuji Maeda, Saburo Sakaki and Masahiro Sakanaka: "An 18-mer peptide fragment of prosaposin ameliorates place navigation disability, cortical infarction, and retrograde thalamic degeneration in rats with focal cerebral ischemia"Journal of Cerebral Blood Flow and Merabolism. 19. 298-306 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Junya Tanaka, Kazuko Toku, Masahiro Sakanaka and Nobuji Maeda: "Morphological differentiation of microglial cells in culture : Involvement of insoluble factors derived from astrocytes"Neuroscience Research. 34. 207-215 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kazuko Toku, Junya Tanaka, Shiro Fujikata, Yuichiro Hamamoto, Yoko Horikawa, Ken'ichi Miyoshi, Norihiko Tateishi, Yoji Suzuki and Nobuji Maeda: "Distinctions between microglial cells and peripheral macrophages with regard to adhesive activities and morphology"Journal of Neuroscience Research. 57. 855-865 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Junya Tanaka, Kazuko Toku, Bo Zhang, Ken Ishihara, Masahiro Sakanaka and Nobuji Maeda: "Astrocytes prevent neuronal death induced by reactive oxygen and nitrogen species"Glia. 28. 85-96 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakatsuka H, Ohta S, Tanaka J, Toku K, Kumon Y, Maeda N, Sakanaka M, Sakaki S: "Release of cytochrome c from mitochondria to cytosol in gerbil hippocampal CAL neurons after transient forebrain ischemia"Brain Res. 849. 216-219 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakatsuka H, Ohta S, Tanaka J, Toku K, Kumon Y, Maeda N, Sakanaka M, Sakaki S: "Cytochrome c release from mitochondria to the cytosol was suppressed in the isehemia-tolerance-induced hippocampal CAL region after 5-min forebrain ischemia in gerbils"Neurosci Lett. 278. 53-56 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Igase K,Tnaka J,et al.: "An 18-mer peptide fragment of prosaposin ameliorates place navigation desability..."Journal of Cerebral Blood Folw and Metabolism. 19. 298-306 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tanaka J,Toku K et al.: "Morphological defferentiation of microglial cells in culture:Involvement of insoluble"Neuroscience Research. 34. 207-215 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tanaka J.Toku K et al.: "Astrocytes prevent neuronal death induced by reactive oxygen and nitrogen species."Glia. 28. 85-96 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Toku K,Tanaka J,et al.: "Microglial cells prevent nitric oxide-induced neuronal apoptosis in vitro"Journal of Neuroscience Research. 53. 415-425 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nakatuka H,Ohta S,Tanaka J,et al.: "Release of cytochrome c from mitochondria to cytosol in gerbil hipppocampal CA1..."Brain Research. 849. 216-219 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nakatuka H,Ohta S,Tanaka J,et al.: "Cytochrome c release from mitochondria to the cytosol was suppressed in..."Neuroscience Letters. 278. 53-56 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kazuko Toku,Junya Tanaka,et al.: "Microglial cells prevent nitric oxide-induced neuronal apoptosis in vitro." Journal of Neuroscience Research. 53. 415-425 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tong-Chun Wen,Junya Tanaka et al: "Interleukin 3 prevents delayed neuronal death in the hippocampal CA1 field" Journal of Experimental Medicine. 188. 635-649 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Junya Tanaka,Kazuko Toku et al.: "Induction of resting microglia in culture medium devoid of glycine and serine" Glia. 24. 198-215 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Lihua Yang,Junya Tanaka et al.: "Astrocytes modulate nitric oxide production by microglial cells through secretion of serine and glycine" Biochemical and Biophysical Research Communication. 251. 277-282 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Satoko Sudo,Junya Tanaka et al.: "Neurons induce the activation of microglial cells in vitro." Experimental Neurology. 154. 499-510 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Keiji Igase,Junya Tanaka et al.: "An 18-mer peptide fragment of prosaposin ameliorates place navigation disability,cortical infarction,and retrograde thalamic degeneration in rats with focal cerebral ischemia." Journal of Cerebral Blood Flow and Metabolism. in press.

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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