2015 Fiscal Year Final Research Report
Analysis of prion protein in microglia/macrophages in the pathophysiology of prion disease
| Project/Area Number |
25450447
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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 |
Veterinary medical science
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| Research Institution | University of the Ryukyus |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Keywords | プリオン / 酸化ストレス / マクロファージ / ミクログリア / 貪食能 / 8-OHdG / ニトロチロシン / iNOS |
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| Outline of Final Research Achievements |
One of the main characteristics of prion diseases, which makes them distinct from bacterial and viral infections, is the absence of an inflammatory reaction. However, recent studies have shown that microglia, macrophage-like cells found in the brain, become activated after prion infection thereby initiating an inflammatory response. Here, we have studied on the physiological role of microglia/macrophages in the pathogenesis of prion diseases. Immunohistochemistry of prion-infected mouse brain showed vacuolar degeneration and the accumulation of PrPSc. PrPSc accumulation was especially evident in astrocytes, which express high levels of iNOS. In addition, microglia showed increased expression of NOX2. Moreover, prion infection increased oxidative stress injury markers including 8-OHdG and nitrated proteins in the brain. Studies using a PrP-deficient macrophage cell line and primary cultures showed a positive correlation between PrP expression and phagocytotic activity.
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| Free Research Field |
ウイルス学
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