| Co-Investigator(Kenkyū-buntansha) |
SHOJI Mikiko OKAYAMA UNIVERSITY, NEUROLOGY, ASSISTANT PROFESSOR, 医歯学総合研究科, 助教授 (60171021)
YOKOO Hideaki GUNMA UNIVERSITY, HUMAN PATHOLOGY, ASSISTANT, 大学院・医学系研究科, 助手 (40282389)
|
|---|
| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
|
|---|
| Research Abstract |
It has been reported that there is microglial involvement in the process of human tauopathies, including Alzheimer's disease, and α-synucleinopathies, comprising Parkinson's disease. To investigate the mechanism and role of microglial activation in a transgenic mouse model of human tauopathies and α-synucleinopathies, we performed pathological analyses of brains from human tauopathies and α-synucleinopathies and the transgenic mouse model. In the TgTauR406W 21807 line, microgliosis correlated with prominent tau accumulation. APPsw mice (Tg2576) showed first appearance of premature, cored plaques at 7-8 months old. Double immunofluprescence staining using both the anti-AβN1 (D) antibody and DAPI demonstrated that round cellular Aβ deposits was nucleus and partly cytoplasma of some peripheral cells around central cores, which were neuronal cells or microglial cells. In brains from human α-synucleinopathies, α-synuclein-positive inclusions were absent in microglia, unlike neurons, oligodendroglia and astrocytes. In α-synucleinopathies, microglial activation almost paralleled the distribution of α-synuclein positive inclusion. MSR-A, a known phagocytosis-associated receptor, was found in a small number of activated microglia, and the clusters of activated microglia, including the phagocytic type, labeled with anti-MHC class II and MSR-A were observed around dying neurons. Our study indicated that microglial activation, including phagocytosis, could be system-specific in tauopathoies and α-synucleinopathies, and that direct contribution of intracellular tau or α-synuclein aggregation to microglial activation could be unlikely.
|
