| Project/Area Number |
62304040
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| Research Category |
Grant-in-Aid for Co-operative Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Neurology
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| Research Institution | Niigata University |
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Principal Investigator |
IKUTA Fusahiro Brain Research Institute, Niigata University, Department of Experimental Neuropathology, Director and Professor, 脳研究所, 教授 (20018592)
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| Co-Investigator(Kenkyū-buntansha) |
TOYOKURA Yasuo Tokyo metropolitan Geriatric Hospital, Director, 院長, 東京大学名誉教授 (50009875)
IHARA Yasuo Tokyo Metropolitan Institute of Gerontology, 2nd Laboratory of Clinical Physiolo, 臨床第2生理, 室長 (60114386)
MANNEN Toru University of Tokyo, Faculty of Medicine, Department of Neurology, Professor, 医学部, 教授 (10010208)
NAGAI Yoshitaka University of Tokyo, Faculty of Medicine, Department of Biochemistry, Professor, 医学部, 教授 (80072974)
TOMONAGA Masanori University of Tokyo, Faculty of Medicine, Department of Neuropathology, Professo, 医学部, 教授 (10072977)
伊藤 正男 東京大学, 医学部, 教授 (90009887)
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| Project Period (FY) |
1987 – 1989
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| Project Status |
Completed (Fiscal Year 1989)
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| Budget Amount *help |
¥14,000,000 (Direct Cost: ¥14,000,000)
Fiscal Year 1989: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1988: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1987: ¥5,900,000 (Direct Cost: ¥5,900,000)
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| Keywords | Neuronal degeneration / Brain lesion repair / Neuronal regeneration / Alzheimer's disease / Astrocyte / Bunina body / Large neurons / Ganglioside / Sprouting / GFAP / 神経細胞機能 / 機能修復 |
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| Research Abstract |
The aim of this research is to elucidate the mechanisms of lesion repair in the neurodegenerative conditions, in which neurons degenerate, and eventually die and disappear in the brain, and is to search for the way to support or maintain the brain function. Our three-year plan for the project appeared to result in success.
Tomonaga demonstrated that Alzheimer's disease brain extract stimulated the survival of cerebral cortical neurons from neonatal rats; Alzheimer's brain extract contained 4-fold neurotrophic activity of normal brain extract. Subsequently, it was concluded that the neurotrophic action of Alzheimer's brain extract was due to the loss of inhibitory factors for survival and neurite formation of cerebral cortical neurons. Ihara disclosed that paired helical filaments observed in the Alzheimer's brain contained phosphorylated tau polypeptide as a major antigenic determinant. Using antibodies to human tau, he revealed massive somatodendritic sprouting of cortical neurons in A
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lzheimer's disease. This fact was further confirmed biochemically; MAP 5, a embryonal microtuble-associated protein, was bound to the paired helical filaments. Ikuta showed morphometrically that in Alzheimer's disease significant and selective decrease of large neurons occurred in the neostriatum, indicating that this nucleus was also exposed to the disease process. His ultrastructural study also suggested that Bunina bodies, characteristic cytoplasmic inclusions in the remaining lower motor neurons in motor neuron disease, might be derived from the endoplastic reticulum, being of great interest in considering the pathogenesis of motor neuron disease. Mannen studied the distribution of beta protein precursor in the Alzheimer's brain and showed that the amount of this protein did not increase in the disease. Kumanishi obtained a CDNA fragment of human GFAP. As the nucleotide sequence of this clone possessed 85.7% homology with that of the mouse GFAP, this clone was identified as one encoding human GFAP. Using the techniques of molecular biology, he is now studying the relationship of neuronal loss with astrocytosis in the human brain. Hirai examined the Alzheimer's brain immunohistochbmically using antibodies to amyloid beta protein and revealed widespread particular senile plaques in both cerebrum and cerebellum. Now, he is also studying the problem of neuronal cell death biochemically. Nagai found that a tetrasialoganglioside, GQlb, promoted neurite outgrowth when added in nanomolar concentrations to cells from two human neuroblastoma cell lines. Based on this finding, he subsequently discovered a new type of biosignal transduction that was mediated through cell surface carbohydrate recognition (ecto biosignal transduction system). Toyokura examined the aged and demented brains and revealed that there was apparent difference in the degree of neuronal loss in the lateral occipitotemporal gyrus between the two groups. Ito analyzed the mechanisms responsible for long-term depression in the cerebellum.
These results obtained by this research group must be important in further studies in the field of neuroscience dealing with the neurodegenerative conditions, including aging and Alzheimer's disease, and their lesion repair. Less
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