1994 Fiscal Year Final Research Report Summary
Multi-disciplinary Approach of Pathophysiology of ALS
| Project/Area Number |
05044161
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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, Professor, 医学部, 教授 (10204976)
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| Co-Investigator(Kenkyū-buntansha) |
DAUBE J. 米国, メイヨー医科大, 教授
MILLS K. 連合王国, オックスフォード大学・医学部, 講師
EISEN A. カナダ, ブリティシュコロンビア大学・医学部, 教授
KOHARA Nobuo Department of Neurology, Assistant, 医学部, 助手 (20252439)
KAJI Ryuji Department of Neurology, Lecturer, 医学部, 助手 (00214304)
EISEN Andrew British Colimbia University, Professor
MILLS Kerry Oxford University, Lecturer
DAUBE Jasper Mayo Medical School, Professor
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| Project Period (FY) |
1993 – 1994
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| Keywords | ALS / multifocal motor neuropathy / fasciculation / familial / central motor program / dystonia / K channel / discharge probability |
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| Research Abstract |
We have conducted a series of research projects on pathophysiology of ALS and related disorders as well as a basic study on central motor control, which is expected to help understand ALS.
1) Study of pathophysiology of multifocal motor neuropathy (MMN), a disorder simulating ALS.
In collaboration with Professor J Daube, we examined the effect of anti-GM1 antibody, which is pathognomonic of MMN,on saltatory conduction in single myelinated nerve fibers in vivo.
2) Study of fasciculation in ALS
We found that some fasciculations in ALS can be evoked by magnetic cortical stimulation. Lack of their voluntary activation or H-reflex activation favors their origin in the upper motor neurons.
3) Study of discharge probability of spinal motoneurons in ALS.
We studied the discharge probability of spinal motoneurons using peri-stimulus time histograms (PSTHs). Markedly increased firing probability was found for the direct corticospinal tract-evoked discharges (primary peak). This may indicate that excitotoxicity caused by glutamate may be the cause of these fasciculations.
4) Study on central motor physiology
Using contingent negative variation (CNV), We studied the central motor program in patients with dystonia, and found that a specific motor program in lost in this disease condition. We also found the importance of gamma efferent systems in producing symptoms in this disease.
5) Genetic study of familial ALS
We found Leu 106-Val (CTG-GTC) mutation of superoxide dysmutase gene in a Japanese patient with familial ALS.
6) Study on ion channels in ALS
In collaboration with Drs J Rothwell and Bostock in National Institute of Neurology, Queen Square, London, we developed a clinical test of threshold electrotonus which reveals functions of potassium and sodium channels in nerves. We also confirmed that some patients with ALS have abnormal potassium channels in the internodes.
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