Multi-disciplinary Approach of Pathophysiology of ALS

ALS 病理生理学的多学科方法

• 批准号: 05044161
• 负责人: KIMURA Jun
• 金额: $ 4.8万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for international Scientific Research
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-05044161/
• 关键词: ALS; multifocal motor neuropathy; fasciculation; familial; central motor program; dystonia; K channel; discharge probability; fasciculation; 大脳磁気刺激; CNV; ジストニア; シナプトフィジン; リルゾール; グルタミン酸

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 ALSWe 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 physiologyUsing 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 ALSWe found Leu 106-Val (CTG-GTC) mutation of superoxide dysmutase gene in a Japanese patient with familial ALS.6) Study on ion channels in ALSIn 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.

我们已经进行了一系列有关ALS和相关疾病病理生理学的研究项目，以及一项有关中央运动控制的基础研究，有望帮助理解ALS。体内的髓神经纤维。2）ALSWE中心的研究发现，磁皮质刺激可以引起ALS中的某些偶像。缺乏自愿激活或H反射激活有利于其在上运动神经元中的起源。3）研究Als中的脊柱运动神经元的放电概率。我们研究了使用刺激性时间表直方图（PSTHS）研究了脊柱运动神经元的放电概率。发现直接皮层脊髓诱发的放电（主要峰）的发射概率显着增加。这可能表明由谷氨酸引起的兴奋性可能是这些症状的原因。4）研究中央运动生理学的研究，涉及偶然性负变异（CNV），我们研究了肌张力障碍患者的中央运动计划，并发现在这种疾病疾病中丢失的特定运动程序。我们还发现，γ屈服系统在这种疾病中产生症状的重要性。5）家族性Alswe的遗传研究发现，在日本家族性ALS的日本患者中，超氧化物d症障碍酶基因的LEU 106-VAL（CTG-GTC）突变是对家族性ALS的日本患者的遗传研究。阈值电孔揭示神经中钾和钠通道的功能。我们还确认，一些ALS患者在节间中有异常的钾通道。

项目成果

Kawamata J et al: "Len 106-Val (CTG-GTC) mutation of superoxide dysmutase in a patient with familial ALS in Japan" Lancet. 343. 1501- (1994)

Kawamata J 等人：“日本家族性 ALS 患者中超氧化物歧化酶的 Len 106-Val (CTG-GTC) 突变”《柳叶刀》。

Kaji R et al: "Tonic vibration reflex and muscle afferent block in writer's cramp" Ann Neurol. (in press). (1995)

Kaji R 等人：“作家痉挛中的强直振动反射和肌肉传入阻滞”Ann Neurol。

Watanabe T et al.: "Ultra-high dose methylcobalamin promotes nerve regeueration in experimental acrylamide neuropathy" J.Neurol.Sci. 122. 140-143 (1994)

Watanabe T 等人：“超高剂量甲钴胺促进实验性丙烯酰胺神经病中的神经再生”J.Neurol.Sci。

Kawamata J et al: "Leu 106-Val(CTG-GTC) mutation of superoxide dismutuse in a natient with famialinl ALS in Japan" Lancet. 343. 1501 (1994)

Kawamata J 等人：“日本家族性 ALS 患者中超氧化物歧化酶的 Leu 106-Val(CTG-GTC) 突变”《柳叶刀》。

Mezaki T et al.: "Comparison of therapeutic efficacies of types A and F botulinum toxins for blepharospasm" Neurology. 45(in press). (1995)

Mezaki T 等人：“A 型和 F 型肉毒毒素治疗眼睑痉挛的疗效比较”神经病学。