| Project/Area Number |
14370102
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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 |
Virology
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| Research Institution | Osaka University |
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Principal Investigator |
IKUTA Kazuyoshi Osaka University, Research Institute for Microbial Diseases Virology, Professor, 微生物病研究所, 教授 (60127181)
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| Co-Investigator(Kenkyū-buntansha) |
TOMONAGA Keizo Osaka University, Research Institute for Microbial Diseases, Virology, Associate Professor, 微生物病研究所, 助教授 (10301920)
TSUJI Shotaro Osaka University, Research Institute for Microbial Diseases, Virology, Research Associate, 微生物病研究所, 助手 (30285192)
TANIYAMA Hiroyuki Rakuno Gakuen University, School of Veterinary Medicine, Veterinary Pathology, Professor, 獣医学部, 教授 (90133800)
小野 悦郎 北海道大学, 遺伝子病制御研究所, 助教授 (00160903)
小林 剛 大阪大学, 微生物病研究所, 助手 (90324847)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥13,400,000 (Direct Cost: ¥13,400,000)
Fiscal Year 2004: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2003: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥7,000,000 (Direct Cost: ¥7,000,000)
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| Keywords | Borna disease virus / central nervous system / transgenic mouse / persistent infection / psychiatric disorder / stress / HMGB1 / phosphoprotein / 神経変性疾患 / パーキンソン病 / アルツハイマー病 / 運動器障害 / 熱ショック蛋白質 / RAGE / リン酸蛋白質 / 加齢 / 神経網 |
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| Research Abstract |
Borna disease virus(BDV) is a highly neurotropic, negative-, single-stranded RNA virus and is the etiological agent of Borna disease, encephalitis in horses and sheep. Infection with BDV in humans, especially in some of the patients with psychiatric disorders, was reported. In fact, BDV signals were identified in some of the autopsied brains from the BDV-seropositive patients. The objective in this study is to analyze the BDV virulence at in vivo and in vitro levels as well as molecular level in order to clarify the mechanism of BDV-induced pathogenesis at the central nervous system. Studies using neuronal cell cultures, revealed 1)the interaction between BDV p24 phosphoprotein (P) and multi-functional protein HMGB1 (also named amphoterin) ; 2)blocking of functions of HMGB1 by the interaction with P protein ; and 3)significant decrease of host anti-stress (such as heating) responses. In addition, we found that neurological symptoms were induced in the rats by stress (intraperitoneal injection with LPS) under the condition with persistent infection with BDV. Further, we prepared transgenic mice expressing BDVP protein under the GFAP promoter in the brain and found that the transgenic mice showed aggressive behavior and significant impairement of spatial reference memory, but no significant effect in the locomotor activity. These transgenic mice also showed the significant decreases in the levels of brain-derived neurotrophic factor(BDNF), synapse density, serotonin receptors (5-THR_<1A> and 5-THR_<1B>) in the brains. Thus, using several model systems, it was clarified that the CNS pathogenesis could appear by the persistent infection with BDV in the CNS.
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