Molecular pathology in viral neurophathogenesis of developmental brain disorders
| Project/Area Number |
15390126
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
TSUTSUI Yoshihiro Hamamatsu University School of Medicine, Professor, 医学部, 教授 (50073135)
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| Co-Investigator(Kenkyū-buntansha) |
KOSUGI Isao Hamamatsu University School of Medicine, Associate Professor, 医学部, 助教授 (10252173)
TSUCHIDA Takashi Hamamatsu University School of Medicine, Research Associate, 医学部, 助手 (30317755)
馬場 聡 浜松医科大学, 医学部, 助教授 (10242760)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2005: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2004: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2003: ¥6,700,000 (Direct Cost: ¥6,700,000)
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| Keywords | viral encephalopathy / cytomegalovirus / developmental disorders / neural stem / progenitor cells / latent infection / transgenic mice / embryonic stem cells / neurosheres / 神経幹細胞 / 大脳スライス培養 / 持続感染 |
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| Research Abstract |
Developing brains are highly susceptible to cytomegalovirus infection, causing developmental brain disorders. Brain disorders are also induced by reactivation of the virus in immune-compromised patients. In order to certify the hypothesis that latent CMV infection occurs in the brains, neonatal mice were infected with murine CMV (MCMV) and raised for a long time and removed the brains. Reactivation was observed in the brain slice cultures. For further analysis, nestin-promoter-GFP inserted transgenic (Tg) mice (provided Dr.H.Okano, Keio Univ.) were latently infected with MCMV. Immature neural cells cultures in the presence of ganciclovir (GCV), then, neurospheres were isolated. We demonstrated that infective virus is released from the neurospheres by plaque assay. This fact indicates that latent infection may occur in neural stem/progenitor cells. We have showed that neurons tend to become persistent infection and that neuronal expression of the early gene e1-promoter was observed in the transgenic mice. We investigated the effect of MCMV infection on the expression of NMDA rece ptors that are essential for the plasticity of synapses and neuronal excito-toxicity. We showed that expression of NMDA receptors were reduced by MCMV infection, probably relating to establish persistent infection and causing functional disorders. Furthermore, in contrast to neural stem/progenitor cells, we showed that embryonic stem (ES) cells are not susceptible to MCMV infection but acquired the susceptibility during the glial differentiation.
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Report
(4 results)
Research Products
(24 results)
