| Project/Area Number |
02454294
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Psychiatric science
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| Research Institution | Hyogo College of Medicine |
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Principal Investigator |
MIYOSHI Koho Hyogo College of Medicine, Department of Neuropsychiatry, Professor, 医学部, 教授 (10068447)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAUCHI Shigeru Hyogo College of Medicine, Department of Neuropsychiatry, Instructor, 医学部, 講師 (60122321)
SATO Masayasu Hyogo College of Medicine, Department of Neuropsychiatry, Instructor, 医学部, 講師 (50115854)
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| Project Period (FY) |
1990 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1992: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1991: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1990: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Protease Inhibitor / Leupeptin / E-64 / Neuritic Plaques / Alzheimer's Disease / Alpha-1-antichymotrypsin / Neuroaxonal Changes / Learning Impairment |
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| Research Abstract |
1. Intracerebroventricular injection of protease inhibitor, leupeptin, and E-64, induced swelling and degeneration of neuronal axon in injected sites, which were closely similar to the neuronal changes in the neuritic plaques of Alzheimer's diseae. Alpha-1-antichymotrypsin, the protease inhibitor, which was demonstrated immunohistochemically in the neuritic plaques, caused characteristic neuroaxonal changes in the spinal cord in rats.
2. Leupeptin showed stimulating and toxic effects of proliferation of axons in the cultured neuronal cells.
3. Intracerebroventricular administration of leupeptin, protease inhibitor, caused a significant learning impairment in passive avoidance test in rats.
Neuroaxonal changes, induced by protease inhibitor, were closely similar to the axonal changes in the vicinity of amyloid core in neuritic plaques. The neuronal changes by leupeptin administration caused a learning impairment in animals. Results of the present studies indicated the importance of protease inhibitor to from a specific neuritic changes in neuritic plaques in Alzheimer's disease.
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