| Project/Area Number |
07044252
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
KIMURA Jun Department of Neurology, KYOTO UNIVERSITY,Professor, 医学研究科, 教授 (10204976)
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| Co-Investigator(Kenkyū-buntansha) |
GRAFE Peter Universitat Munchen, Professor, 生理学研究所, 教授
BOSTOCK Hugh University of London, Professor, 神経研究所, 教授
QUASTHOFF Stephen Neurologische Klinik und Poliklinik der Technischen Universitat, Lecturer, 医学部, 講師
CORNBLATH David Johns Hopkins University, Professor, 医学部, 教授
ENGLAN John Louisiana State University, Professor, 医学部, 準教授
SUMMER Austin Louisiana State University, Professor of Chairman, 医学部, 主任教授
ROWLAND Lewis Columbia University, Professor of Chairman, 医学部, 主任教授
MURRAY Nicholas The National Hospital for Neurology and Neurosurgery, Professor, 部長
DAUBE Jasper Mayo Medical School, Professor, 部長
EISEN Andrew British Columbia University, Professor, 医学部, 教授
KOHARA Nobuo Department of Neurology, KYOTO UNIVERSITY,Assistant, 医学研究科, 助手 (20252439)
KAJI Ryuji Department of Neurology, KYOTO UNIVERSITY,Lecturer, 医学研究科, 講師 (00214304)
AKIGUCHI Ichiro Department of Neurology, KYOTO UNIVERSITY,Associate Professor, 医学研究科, 助教授 (30115779)
BURKE David シドニー大学, 医学部, 教授
ROTHWEV John 連合王国国立神経病院, 神経科, 部長
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥12,900,000 (Direct Cost: ¥12,900,000)
Fiscal Year 1996: ¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 1995: ¥6,800,000 (Direct Cost: ¥6,800,000)
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| Keywords | ALS / Threshold Electrotonus / Magnetic Brain Stimulation / PSTH / fasciculation / K^+ channel / Multifocal Motor Neuropathy / glutamate / Multifocal Motor Meuropathy / motor neuron disease / methylcobalamin / magnetic stimulation / threshald electrotonus / K^+ channel |
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| Research Abstract |
The pathophysiology of ALS remains unknown because of the lack of appropriate clinical measures of disease process. Electrophysiological methods provide a useful means of analyzing the pathomechanisms of not only the clinical findings such as fasciculations but also the disease progression. We have developed two innovative electrophysiological testings in this project. One is PSTH (persistimulus time histogram) analysis of single motor unit after magnetic stimulation of the motor cortex, which revealed increased excitability of the cortical motoneurone and virtually larger than normal EPSP at the synapse on the spinal motoneurone in ALS,which supports the glutamate-induced neuroexcitatory theory. The other method is threshold electrotonus (TE), which records membrane potential changes and potassium channel function in human subjects. The latter revealed abnormal quantity and quality of the channels in ALS,which accounts for the peripherally-generated fasciculations.
Taking these findings together, we postulate a hypothesis on the pathogenesis of ALS.It is likely that ALS is caused by various primary causes, which share the final common mechanism of cell death. Apoptosis or programd cell death, characterized by DNA fragmentation in the nucleus, has been focused in this regard, Glutamate excitotoxicity, serum or growth factor withdrawal, calcium ionophores, free radical inducing agents, heavy metals including methyl mercury are all known to trigger apoptosis, and are among the possible primary causes. If the phylogenetically newest corticospinal system is the most prone to such gene modification during the long life of a neuron, the sparing of extraocular muscles and sphincters would be explained.
These patients suffer from the loss of the most sophisticated part of the human nervous system, which subserves dexterity of human movement enabling the use of tools. In this sense, the patients with ALS may be regarded as victims of phylogenetic development.
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