2005 Fiscal Year Final Research Report Summary
The role of Fc receptors in microglial activation and excototoxic neuronal death.
| Project/Area Number |
16591140
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | Okayama University |
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Principal Investigator |
OKAMOTO Motoi Okayama University, Medical School, Professor, 医学部, 教授 (80144757)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIKAWA Tetsuya Okayama University, Medical School, Assistant Professor, 医学部, 助教授 (90221754)
USUI Shinichi Okayama University, Medical School, Assistant, 医学部, 助手 (50346417)
SATO Hiaki Okayama University, Medical School, Assistant, 医学部, 助手 (70362960)
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| Project Period (FY) |
2004 – 2005
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| Keywords | excitotoxic neuronal death / mouse / kainic acid / hippocampus / pyramidal cell loss / FcR-deficient mouse / microglia / astrocyte |
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| Research Abstract |
The role of IgG Fc receptors in microglial activation and excitotoxic neuronal death was examined in the mouse deficient of γ subunit of FcγRIII (FcRγ-/-), or FcγRIIB (FcγRIIB-/-). Both FcRγ-/- and Fc γRIIB-/- were extremely sensitive to systemic administration of kainic acid (KA) as well as wild type mouse C57BL/6J. However, the duration of convulsive status was significantly shorter in FcR-deficient mouse than C57BL/6J. In addition, appearance of activated microglia and reactive astrocyte was poor in FcR-deficient mousse suggesting that Fc receptors contribute to maintenance of convulsive seizures and activation of microglia and astrocyte.
In FcR-deficinet mouse, pyramidal cell loss following intrahippocampal KA injection was significantly mild compared to C57BL/6J in which moderate pyramidal cell loss occurred within 24 hours following KA injection. Because expression of IL-6,IL-1β,TNF-α reached a peak at 4 hours after KA injection in FcR-deficient mouse whereas IL-6,IL-1β were more persistently expressed in C57BL/6J, Fc receptors contribute to regulation of cytokine expression and hence pyramidal cell loss following excitotoxic stimuli. In addition, primary culture of mouse forebrain neurons and astrocyte has been established to investigate molecular mechanism of the role of Fc receptors and microglia.
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