| Co-Investigator(Kenkyū-buntansha) |
VINCENT Steven R. Associate Professor, Department of Neurology, The University of British Columbia, コロンビア州立大学・神経学(カナダ), 準教授
MCGEER Edith G. Emeritus Professor, Department of Neurology, The University of British Columbia, コロンビア州立大学・神経学(カナダ), 名誉教授
MCGEER Patrick L. Professor, Department of Neurology, The University of British Columbia, コロンビア州立大学・神経学(カナダ), 教授
FUJIMIYA Mineko Research Associate, Department of Anatomy, Shiga University of Medical Science, 医学部, 助手 (10199359)
TOOYAMA Ikuo Research Associate, Molecular Neurobiology Research Center, Shiga University of, 分子神経生物学研究センター, 助手 (20207533)
KANAI Kazumitsu Assistant Professor, Molecular Neurobiology Research Center, Shiga University of, 分子神経生物学研究センター, 助教授 (40108642)
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| Research Abstract |
Alzheimer's disease is diagnosed by the presence of massive senile plaques and neurofibillary tangles. In addition to these classical pathology, recent evidence indicates that the disease is suffered from a specific cholinergic neuronal loss in the substantia innominata. Since this cholinergic system provides the major cholinegic regalation in the cerebral cortex, and since cortical cholinergic functions are deeply associated with higher brain functions such as cognition, memory and learning, our project team aimed to clarify cholinergic systems in Alzheimer disease. The project was focused, in particular, some abnormal expression of various neuroactive substances in the brain, possibly due to the deterionation of genes specifically occurring in this disease. Drs. P. L. McGeer, E. G. McGeer and I. Tooyama found that fibroblast growth factor is hyperexpressed in astrocytes surrounding senile plaques in Alzheiner disease. This growth factor is now well accepted to have potential activity
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for neuronal cell maintainance. Drs. McGeers and K. Hanai clarified that fibroblast growth factor receptors are expressed dynamically along with, the progress of the disease. Dr. M Fujimiya, working together with Professor John C Brown, Department of Physiology, The University of British Columbia, has established a unique method for analysing peripheral cholinergic system. The method, termed "Isolated perfusion system of the intestine, " allowed us to study cholinergic role on gut paraneuron function. Dr. S. R. Vincent and the principal investigator published a paper entitled "Mapping of Nitric oxide synthase in the rat brain. " This paper is originally based on NADPH-diaphorase histochemistry. lncidentally, Dr. Vincent determined that the NADPH-diaphorase is identical with nitric oxides synthase(NOS). This finding is very important, since the cholinergic neurons in the pedunculopontine tegmental nucleus is virtually all NADPH-diaphonase-positive and thus NOS-positive. These cholinergic neurons are shown, by us, that the enzyme expression is prohibited with aging. Our hypothesis, at present, is that Alzheimer disease is a disease which is primarily affected on the living maintenance of various neurons, including cortical cells and subcortical cholinergic cells. With the progress of the disease, protective mechanisms including neurotrophic factors are expressed, but the failure of such protection after all lead the secondary degenerations like senile plaques and tangles. Less
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