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Roles of Glial Cells for Neurodegeneration in Prion Diseases

Research Project

Project/Area Number 15380202
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Basic veterinary science/Basic zootechnical science
Research InstitutionOsaka Prefecture University

Principal Investigator

NAKAMURA Yoichi  Osaka Prefecture University, Grad.School of Life and Environmental Sciences, Lab. of Integrative Physiology in Veterinary Science, Professor, 生命環境学研究科, 教授 (90180413)

Co-Investigator(Kenkyū-buntansha) MORIYAMA Mitsuaki  Osaka Prefecture University, Grad.School of Agriculture and Biological Sciences, Lab. of Integrative Physiology in Vet.Science, Associate Professor, 生命環境学研究科, 助教授 (20275283)
FUJIMOTO Yuka  Osaka Prefecture University, Grad.School of Agriculture and Biological Sciences, Lab. of Integrative Physiology in Vet.Science, Assistant Professor, 生命環境学研究科, 助手 (40405361)
KANNAN Yukiko  Osaka Prefecture University, Grad.School of Agriculture and Biological Sciences, Lab. of Integrative Physiology in Vet.Science, Guest Investigator, 生命環境学研究科, 客員研究員 (80264810)
Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥13,000,000 (Direct Cost: ¥13,000,000)
Fiscal Year 2005: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2004: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 2003: ¥5,800,000 (Direct Cost: ¥5,800,000)
KeywordsMicroglia / Astrocyte / EC-SOD / Amphotericin B / NOS / NO production / プリオン断片 / 一酸化窒素 / アミロイド断片 / 血清成分 / リポ蛋白 / βアミロイド / コレステロール
Research Abstract

It is unknown how affects Amphotericin B (AmB), reported to be a therapeutic drug against prion diseases, on microglial function. Cultured microglia prepared from rat new-born brain were stimulated to produce nitric oxide (NO) by prion peptide (106-126) (PrP), and also by AmB. The level of the NO production stimulated by AmB was enhanced by the presence of the PrP. These results suggest a certain interaction between AmB and PrP and the interaction modulates the microglial cell function. The elucidation of this interaction might be a key for the therapeutic mechanism of AmB against prion diseases.
The physiological functions of prion protein is speculative; however, it is suggested that prion protein is involves in the, mechanism of Cu transport, which is an essential metal for superoxide dismutase (SOD), through cell membrane. We have established the method for the measurement of extracellular SOD (EC-SOD) activity in the living cells. The activities of EC-SOD of cultured astrocytes from rat embryo's brain decreased to a half after stimulation by lipopolysaccharide (LPS) for 24 hr, whereas the intracellular SODs (cytoplasmic and mitochondrial) increased. On the other hand, the activity of SOD in the culture medium increased by LPS dose-dependently. These results suggest that EC-SOD is released from cell surface into the medium. Astrocytes may play an important role for the regulation of brain parenchymal level of active oxygen species by changing localization of EC-SOD ; protecting surrounding neurons from oxidative stress.

Report

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

    (35 results)

All 2006 2005 2004 2003 Other

All Journal Article (29 results) Book (2 results) Publications (4 results)

  • [Journal Article] Potentiation by high potassium of lipopolysaccharide-induced nitric oxide production from cultured astrocytes.2006

    • Author(s)
      Nakamura, Y., Kitagawa, T., Ihara, H., Kozaki, S., Moriyama, M., Kannan.Y
    • Journal Title

      Neurochem Int. 48(1)

      Pages: 43-49

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Regulating factors for induction of nitric oxide synthase in microglia and astrocytes.2006

    • Author(s)
      Nakamura Y.
    • Journal Title

      Degeneration and Regeneration in Neurons, 2006 (ed. by Yoneda and Ogita)( Research Signpost, Kerala, India)

      Pages: 13-36

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Potentiation by high potassium of lipopolysaccharide-induced nitric oxide production from cultured astrocytes.2006

    • Author(s)
      Nakamura, Y., Kitagawa, T., Ihara, H., Kozaki, S., Moriyama, M., Kannan, Y
    • Journal Title

      Neurochem Int. 48(1)

      Pages: 43-49

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Potentiation by high potassium of lipopolysaccharide-induced nitric oxide production from cultured astrocytes.2006

    • Author(s)
      Nakamura, Y., Kitagawa, T., Ihara, H., Kozaki, S., Moriyama.M., Kannan, Y
    • Journal Title

      Neurochem Int. 48(1):

      Pages: 43-49

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Oxidative metabolites are involved in polyamine-induced microglial cell death.2005

    • Author(s)
      Takano, K., Ogura, M., Yoneda, Y., Nakamura Y.
    • Journal Title

      Neuroscience 134(4)

      Pages: 1123-1131

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Neuronal and glial responses to of amine in the ischemic brain2005

    • Author(s)
      Takano, K., Ogura, M., Nakamura, Y., Yoneda, Y
    • Journal Title

      Current Neurovascular Research 2

      Pages: 213-223

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Apparent presence of Serl33-phosphorylated cyclic AMP response element binding protein (pCREB) in brain mitochondria is due to cross-reactivity of pCREB antibodies with pyruvate dehydrogenase.2005

    • Author(s)
      Platenik, Jan., Balcar V.J., Yoneda, Y., Kuramoto, N.Wilczynski, G., Ogita, K., Nakamura, Y., Kaczmarek, L
    • Journal Title

      Neurochem. 95(5)

      Pages: 1446-1460

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Oxidative metabolites are involved in polyamine-induced microglial cell death.2005

    • Author(s)
      Takano, K.Ogura, M., Yoneda, Y., Nakamura Y.
    • Journal Title

      Neuroscience 134(4)

      Pages: 1123-1131

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Neuronal and glial responses to polyamine in the ischemic brain.2005

    • Author(s)
      Takano, K., Ogura, M., Nakamura, Y., Yoneda, Y
    • Journal Title

      Current Neurovascular Research. 2

      Pages: 213-223

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Apparent presence of Ser133-phosphorylated cyclic AMP response element binding protein (pCREB) in brain mitochondria is due to cross-reactivity of pCREB antibodies with pyruvate dehydrogenase.2005

    • Author(s)
      Platenik, Jan., Balcar V.J., Yoneda, Y.,...Kuramoto, N., Wilczynski, G., Ogita, K., Nakamura, Y., Kaczmarek, L.
    • Journal Title

      J Neurochem. 95(5)

      Pages: 1446-1460

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Oxidative metabolites are involved in polyamine-induced microglial cell death. Neuroscience2005

    • Author(s)
      Takano, K.Ogura, M., Yoneda, Y., Nakamura Y.
    • Journal Title

      Neuroscience 134(4)

      Pages: 1123-1131

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Deletion of PPARγ in adipose tissues of mice protects against high fat diet-induced obesity and insulin resistance.2005

    • Author(s)
      Jones, J.R., Barrick, C., Kim, K.A., Lindner, J., Blondeau, B., Fujimoto, Y., Shiota, M., Kesterson, R.A., Kahn, B.B., Magnuson, M.A.
    • Journal Title

      Proc Natl Acad Sci USA,,. 102

      Pages: 6207-6212

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Neuronal and glial responses to polyamine in the ischemic brain2005

    • Author(s)
      Takano, K., Ogura, M., Nakamura, Y., Yoneda, Y
    • Journal Title

      Current Neurovascular Research 2

      Pages: 213-223

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Apparent presence of Ser133-phosphorylated cyclic AMP response element binding protein (pCREB) in brain mitochondria is due to cross-reactivity of pCREB antibodies with pyruvate dehydrogenase.2005

    • Author(s)
      Platenik, Jan., Balcar V.J., Yoneda, Y.,...Kuramoto, N., Wilczynski, G., Ogita, K., Nakamura, Y., Kaczmarek, L
    • Journal Title

      J Neurochem. 95(5):

      Pages: 1446-1460

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Metabolic derangements in deficiency of citrin, a liver-type mitochondrial aspartate-glutamate carrier.2005

    • Author(s)
      Saheki T, Kobayashi K, Iijima M, Moriyama M, Yazaki M, Takei YI, Ikeda SI.
    • Journal Title

      Hepatol Res Sep 28; Epub

    • NAID

      10016809437

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Pyruvate ameliorate the defect in ureogenesis from ammonia in citrin-deficient mice.2005

    • Author(s)
      Moriyama.M., Li, M.X., Kobayashi, K., Sinasac, D.S., Kannan.Y., Iijima, M., Horiuchi, M., Tsui, L-C., Tanaka, M., Nakamura, Y., Saheki, T.
    • Journal Title

      J Hepatol. Nov 8; Epub

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Neuroprotective effects of ONO-1924H, an inhibitor of poly ADP-ribose polymerase (PARP), on cytotoxicity of PC12 cell and ischemic cerebral damage.2004

    • Author(s)
      Kamanaka, Y., Kondo, K., Suzuki, Y., Nakamura, Y., Umemura, K.
    • Journal Title

      Life Sciences 76

      Pages: 151-162

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Neuroprotective effects of ONO-1924H, an inhibitor of poly ADP-ribose polymerase (PARP), on cytotoxicity of PC12 cell s and ischemic cerebral damage.2004

    • Author(s)
      Kamanaka, Y., Kondo, K., Suzuki, Y., Nakamura, Y., Umemura, K.
    • Journal Title

      Life Sciences 76

      Pages: 151-162

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Beneficial effects of troglitazone on neutrophil dysfunction in multiple low-do sestreptozotocin-induced diabetic mice.2004

    • Author(s)
      Y.Kannan, M.Tokunaga, M.Moriyama, H.Kinoshita, Y.Nakamura
    • Journal Title

      Clin.Exp.Immunol 137

      Pages: 263-271

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Slc25A 13-knockout mice display metabolic deficits but fail to show signs of adult-onset type-II citrullinemia (CTLN2).2004

    • Author(s)
      Sinasac, D.S., Moriyama, M., Jalil, M.A., Begum, et al.
    • Journal Title

      Mol.Cell.Biol 24

      Pages: 527-536

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Characteristics of mitochondrial aspartate glutamate carrier (citrin) knockout mice.2004

    • Author(s)
      Moriyama, M.
    • Journal Title

      Vet.Biochem. 41

      Pages: 23-29

    • NAID

      10026882464

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Neuroprotective effects of ONO-1924H, an inhibitor of poly ADP-ribose polymerase (PARP), on cytotoxicity of PC12 cell s and ischemic cerebral damage2004

    • Author(s)
      Kamanaka, Y., Kondo, K.,..., Suzuki, Y., Nakamura, Y., Umemura, K.
    • Journal Title

      Life Sciences 76

      Pages: 151-162

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Microglial cell death induced by a low concentration of polyamines.2003

    • Author(s)
      Takano, K, Nakamura, Y., Yoneda, Y.
    • Journal Title

      Neuroscience 120

      Pages: 961-967

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Adenosine triphosphate inhibits cytokine release freom lipopolysaccharide-activated microglia via P2y receptors.2003

    • Author(s)
      Ogata, T., Chuai, M., Marina, T., Yamamoto, H., Nakamura, Y., Schubert, P.
    • Journal Title

      Brain Research 981

      Pages: 174-183

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Potentiation by ATP of lipopolysaccharide-stimulated nitric oxide production in cultured astrocytes2003

    • Author(s)
      Murakami, K., Nakamura, Y..Yoneda, Y.
    • Journal Title

      Neuroscience 117

      Pages: 37-42

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Involvement of protein kinase C in glutamate release from cultured microglia.2003

    • Author(s)
      Nakamura, Y., Ohmaki, M., Murakami, K., Yoneda, Y.
    • Journal Title

      Brain Res 962

      Pages: 122-128

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Adenosine triphosphate inhibits cytokine release from lipopolysaccharide-activated microglia via P2y receptors.2003

    • Author(s)
      Ogata, T., Chuai, M., Morino, T., Yamamoto, H., Nakamura, Y., Schubert, P.
    • Journal Title

      Brain Research 981

      Pages: 174-183

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Potentiation by ATP of lipopolysaccharide-stimulated nitric oxide production in cultured astrocytes2003

    • Author(s)
      Murakami, K., Nakamura, Y., Yoneda, Y.
    • Journal Title

      Neuroscience 117

      Pages: 37-42

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Involvement of protein kinase C in glutamate release from cultured microglia..2003

    • Author(s)
      Nakamura, Y., Ohmaki, M., Murakami, K., Yoneda, Y.
    • Journal Title

      Brain Res 962

      Pages: 122-128

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] Regulating factors for induction of nitric oxide synthase in microglia and astrocytes. in "Degeneration and Regeneration in Neurons"(ed.by Yoneda, Ogita)2006

    • Author(s)
      Nakamura Y.
    • Total Pages
      24
    • Publisher
      Research Signpost, Kerala, India
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] Regulating factors for induction of nitric oxide synthase in microglia an astrocytes. in "Degeneration and Regeneration in Neurons" (ed. by Yoneda and Ogita)2006

    • Author(s)
      Nakamura Y.
    • Total Pages
      24
    • Publisher
      Research Signpost, Kerala, India
    • Related Report
      2005 Annual Research Report
  • [Publications] Takano, K, Nakamura, Y., Yoneda, Y.: "Microglial cell death induced by a low concentration of polyamines"Neuroscience. 120. 961-967 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ogata, T., Chuai, M., Morino, T., Yamamoto, H., Nakamura, Y., Schubert, P.: "Adenosine triphosphate inhibits cytokine release freom lipopolysaccharide-activated microglia via P2y receptors"Brain Research. 981. 174-183 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Murakami, K., Nakamura, Y., Yoneda, Y.: "Potentiation by ATP of lipopolysaccharide-stimulated nitric oxide production in cultured astrocytes"Neuroscience. 117. 37-42 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nakamura, Y., Ohmaki, M., Murakami, K., Yoneda, Y.: "Involvement of protein kinase C in glutamate release from cultured microglia..,"Brain Res. 962. 122-128 (2003)

    • Related Report
      2003 Annual Research Report

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

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