| Project/Area Number |
11670201
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Human pathology
|
|---|
| Research Institution | Tokyo Metropolitan Institute for Neuroscience |
|---|
Principal Investigator |
KOMORI Takashi Tokyo Metropolitan Institute for Neuroscience, Department of Clinical Neuropathology, Director, 東京都神経科学総合研究所, 副参事研究員 (90205526)
|
|---|
| Project Period (FY) |
1999 – 2002
|
| Project Status |
Completed (Fiscal Year 2002)
|
| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2002: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
|
|---|
| Keywords | multiple system atrophy / progressive supranuclear palsy / oligodendrocyte / astrocyte / cytoplasmic inclusions / cell death / tau / 14-3-3 / 神経細胞死 / タウ蛋白 / グリア細胞 / ピック病 / タウオパチー / 神経細胞変性 / 大脳基底核変性症 / グリア / 剖検脳 |
|---|
| Research Abstract |
To investigate whether glial pathology correlates with neurodegeneration, we studied autopsied material from subjects with neurodegenerative diseases including progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), Pick's disease (PiD) and multiple system atrophy (MSA). Results: 1) Correlation between tau density and cerebral tissue damage were analyzed in 7 PSP. Low negative correlation with MAP-2 or EAAT-1 densities and low positive correlation with CD68 or GFAP densities were obtained. Cerebral tissue injury may be not dependent on the amount of tau in PSP. 2) Hippocampal tau pathology was studied in 6 PSP, 4 CBD and 3 age-matched controls. In PSP and control, neurofibrillary tangles and threads were present in the entorhinal cortex and hippocampus. In CBD, coiled bodies and threads were found in the alveus and stratum lacunosum and tau-positive grains in the inner molecular layer of the dentate gyrus. Hippocampal tau pathology in PSP is similar to that in aged subje
… More
cts whereas that in CBD is distinctive from PSP. 3) Using tyramide signal amplification system on anti-PHF-tau antibody in 5 PiD, ***ead and Pick body-like inclusions were detected in the subcortical white matter. Hyperphosphorylated tau may be localized in the subcortical axons in addition to the dendrites. 4) Immunohistologic examination using microglial markers were studied in13 MSA and disclosed numerous amoeboid microglia phagocytosing degenerating myelin. Such activated microglia were the most prominent in the extrapyramidal and cerebellar input systems. Microglial activation may play a role in the system degeneration of MSA. 5) In 6 MSA, co-localization of 14-3-3-protein and alpha-synuclein immunoreactivities within the GCIs was confirmed on immunohistochemistry. The immunolabeling rate of GCIs with 14-3-3 proteins varied regionally from 40 to 90 %. Negative correlation between tissue degeneration and density of 14-3-3-positive GCIs was present. 14-3-3 proteins may be closely associated with alpha-synuclein in GCIs Less
|
