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The study of neuropathogenesis in the developing brain disorders induced by viral infection

Research Project

Project/Area Number 12470054
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

TSUTSUI Yoshihiro  Hamamatsu University School of Medicine, Professor, 医学部, 教授 (50073135)

Co-Investigator(Kenkyū-buntansha) BABA Satoshi  Hamamatsu University School of Medicine, Associate Professor, 医学部, 助教授 (10242760)
KOSUGI Isao  Hamamatsu University School of Medicine, Research Associate, 医学部, 助手 (10252173)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥11,500,000 (Direct Cost: ¥11,500,000)
Fiscal Year 2002: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2001: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2000: ¥6,500,000 (Direct Cost: ¥6,500,000)
Keywordsviral encephalopathy / cytomegalovirus / transgenic mice / brain slice culture / brain disorder / neural progenitor cells / neural stem cells / トランスゲニックマウス
Research Abstract

We investigated the effects of murine cytomegalovirus (MCMV) infection on the developing mouse brain in terms of susceptible cells and age-related resistance. Mouse brain slices at different development stages were infected with recombinant MCMV in which the lacZ gene was inserted into a late gene. The ventricular zone (VZ) and cortical marginal region were the sites most susceptible to MCMV infection, and the susceptibility declined with the development of the brain. Immunohistochemical staining showed that the virus-susceptible cells were positive for GFAP, nestin and Musashi-1, suggesting the susceptible cells in the VZ are glial progenitor cells. These results suggest that the amount of immature glial cells in the developing brain may be closely associated with the susceptibility of the brain to CMV infection in humans.
We examined the reactivation of latent murine CMV (MCMV) infection in the mouse brain by their transfer to brain slice culture. We infected neonatal and young adult mice intracerebrally with recombinant MCMV. The brains were removed 6 months after infection, and used to prepare brain slices that were then cultured for up to 4 weeks. X-Gal-positive cells were observed in marginal regions of the brains or immature neural cells in the ventricular walls. Immunohistochemical staining showed that the X-Gal-positive reactivated cells were neural stem/progenitor cells. These results suggest that brain disorders may occur long after infection by reactivation of latent infection in the immature neural cells.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] Tsutusi, Y., et al.: "Reactivation of latent cytomegalovirus infection in mouse brain cells detected after transfer to brain slice cultures"Journal of Virology. 76(14). 7247-7254 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kosugi, I., et al.: "Innate Immune Reponses to Cytomegalovirus Infection in the Developing Mouse Brain and Their Evasion by Virus-Infected Neurons"American Journal of Pathology. 161(3). 919-928 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawasaki, H., et al.: "The amount of immature glial cells in organotypic brain slices determines the susceptibility to murine cytomegalovirus infection"Laboratory Investigation. 82(10). 1347-1358 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Li, R-Y., et al.: "Activation of murine cytomegalovirus immediate-early promoter in cerebral ventricular zone and glial progenitor cells in transgenic mice"Glia. 35. 41-52 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kosugi, I., et al.: "Cytomegalovirus infection of the CNS stem cells from mouse embryo : A model for developmental brain disorders induced by cytomegalovirus"Laboratory Investigation. 80(9). 1373-1383 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Li, R-Y., Tsutsui, Y.: "Growth retardation and microcephaly induced in mice by placental infection with murine cytomegalovirus"Teratology. 62. 79-85 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tsutsui Y, Kawasaki H, Kosugi I: "Reactivation of latent cytomegalovirus infection in mouse brain cells detected after transfer to brain slice cultures"Journal of Virology. 76(14). 7247-7254 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kosugi I, Kawasaki H, Arai Y, Tsutsui Y: "Innate Immune Reponses to Cytomegalovirus Infection in the Developing Mouse Brain and Their Evasion by Virus-Infected Neurons"American Journal of Pathology. 161(3). 919-928 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawasaki H, Kosugi I, Arai Y, Tsutsui Y: "The amount of immature glial cells in organotypic brain slices determines the susceptibility to murine cytomegalovirus infection"Laboratory Investigation. 82(10). 1347-1358 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Li R-Y, Baba S, Kosugi I, Arai Y, Kawasaki H, Shinmura Y, Sakakibara S, Okano H, Tsutsui Y: "Activation of murine cytomegalovirus immediate-early promoter in cerebral ventricular zone and glial progenitor cells in transgenic mice"Glia. 35. 41-52 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kosugi I, Shinmura Y, Kawasaki H, Arai Y, Li R-Y, Baba S, Tsutsui Y: "Cytomegalovirus infection of the CNS stem cells from mouse embryo : A model for developmental brain disorders induced by cytomegalovirus"Laboratory Investigation. 80(9). 1373-1383 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Li R-Y, Tsutsui Y: "Growth retardation and microcephaly induced in mice by placental infection with murine cytomegalovirus"Teratology. 62. 79-85 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tsutsui, Y., et al.: "Reactivation of latent cytomegalovirus infection in mouse brain cells detected after transfer to brain slice cultures"Journal of Virology. 76(14). 7247-7254 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kosugi, I., et al.: "Innate Immune Reponses to Cytomegalovirus Infection in the Developing Mouse Brain and Their Evasion by Virus-Infected Neurons"American Journal of Pathology. 161(3). 919-928 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kawasaki, H., et al.: "The amount of immature glial cells in organotypic brain slices determines the susceptibility to murine cytomegalovirus infection"Laboratory Investigation. 82(10). 1347-1358 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kosugi, I.: "Cytomegalovirus infection of the CNS stem cells from mouse embryo : A model for developmental brain disorders induced by cytomegalovirus"Laboratory Investigation. 80(9). 1373-1383 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Li, R-Y.: "Growth retardation and microcephaly induced in mice by placental infection with murine cytomegalovirus"Teratology. 62. 79-85 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Li, R-Y.: "Activation of murine cytomegalovirus immediate-early promoter in cerebral ventricular zone and glial progenitor cells in transgenic mice"GLIA. 35. 41-52 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kosugi,I.: "Cytomegalovirus infection of the CNS stem cells from mouse embryo : A model for divelopmental brain disorders induced by cytomegalovirus."Laboratory Investigation. 80・9. 1373-1383 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Li,R-Y.: "Growth retardation and microcephaly induced in mice by placental infection with murine cytomegalovirus."Teratology. 62. 79-85 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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