| Project/Area Number |
62570488
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Psychiatric science
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| Research Institution | OSAKA UNIVERSITY |
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Principal Investigator |
NISHIMURA Tsuyoshi OSAKA UNIVERSITY MEDICAL SCHOOL, 医学部, 教授 (70028455)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEDA Masatoshi OSAKA UNIVERSITY MEDICAL SCHOOL, 医学部, 助手 (00179649)
TADA Kunitoshi OSAKA UNIVERSITY MEDICAL SCHOOL, 医学部, 助手 (80135681)
HARIGUCHI Shiro OSAKA UNIVERSITY MEDICAL SCHOOL, 医学部, 助教授 (10028459)
NIIGAWA Hisayoshi OSAKA UNIVERSITY MEDICAL SCHOOL (70243227)
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| Project Period (FY) |
1987 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1988: ¥200,000 (Direct Cost: ¥200,000)
Fiscal Year 1987: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | cerebrovascular dementia / Mongolian gerbil / microtubule-associated protein (MAP) 2 / Alzheiemr's diease / aluminium / アルツハイマー病 / カテプシンDグリア線維酸性蛋白 / アルツハイマー型老年痴呆 / cathepsin D / 慢性脳血流低下モデル / microtubule associated protein2(MAP2) |
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| Research Abstract |
Under the purpose of establishing an animal model of cerebrovascular dementia. the bilateral carotid artery of Mongolian gerbil is stenosed with a newly designed clip. showing decreased regional cerebral blood flow to 75 % of the original level for 8 weeks. dysfunction in learning by passive avoidance test. a little morphological evidence of neuronal death in hippocampal caI region. and decreased amount of microtubule-associated protein (HAP) 2.
As a neurochemical model of Alzheiemr's diease. rabbits are injected with aluminium salt. resulting in formation of experimental neurofibrillary change. The rabbit brain with experimental neurofibrillary change is studied and the activity of seven lysosomal enzymes is assaged. showing increased activity of cathepsin D enzyme. The cathepsin D enzyme from the aluminium injected rabbit brain is purified by affinity chromatography. The molecular and emzymological characterization of the pathological cathepsin D shows the same molecular weight. same amino acid composition. but different Km and Vmax values, and different pattern of heat denaturation. Further, the instability of the lysosome membrame is demonstrated in the aged rat brain, which could partially explain the increased activity of cathepsin D in model animal of Alzheimer's disease.
Under the purpose of finding a biological marker of Alzheimer's disease. the serum autoantibody titer to glial fibrillary acidic protein (GFAP) is assayed, showing significantly increased antibody titer to GFAP in Alzheimer's disease patient sera but not in that of the healthy control subjects.
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