| Project/Area Number |
25461285
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Kagoshima University |
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Principal Investigator |
IZUMO Syuji 鹿児島大学, 医歯学域医学系, 教授 (30143811)
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| Co-Investigator(Kenkyū-buntansha) |
KUBOTA RYUJI 鹿児島大学, 医歯学域医学系, 准教授 (70336337)
FURUKAWA YOSHITAKA 医歯学域医学部, 歯学部附属病院, 講師 (00359978)
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| Co-Investigator(Renkei-kenkyūsha) |
MORI KAZYYASU 国立感染症研究所, 研究員 (20270655)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 神経病理学 / ウイルス / 認知障害 / 神経免疫学 |
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| Outline of Final Research Achievements |
To understand the pathogenesis of HIV-1 associated neurocognitive disorders (HANDs) we immunohistochemically analyzed brains from simian immunodeficiency virus (SIV)-macaque models and autopsy brains from HIV-1-infected individuals. A highly virulent SIV302-2-infected animals efficiently developed SIV encephalitis with multinuclear giant cells. Concerning the cortical degenerative changes, astrocyte-specific functional molecules, EAAT-2, AQP4, and connexin43 were proportionally reduced in the frontal cortex, and neuronal, as well as astrocytic, apoptosis was observed. A double immunohistochemistry demonstrated that reduction of AQP4 preceded EAAT-2 reduction, suggesting that a primary damage of astrocyte and blood-brain barrier disturbance induce excitatory neuronal cell death. Menin and TGF-beta were expressed in the apoptotic neurons suggesting their roles in pathogenesis of HANDs. These data confirm two independent pathogenic processes in HANDs.
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