MOTOR NEURON DISEASE--NEUROPHYSIOLOGY AND PATHOLOGY

描述：（改编自申请人摘要）人运动神经元 疾病包括婴儿的遗传性脊肌萎缩， 儿童，成人，肌萎缩侧索硬化症和脊髓灰质炎后 综合征遗传性犬脊髓性肌萎缩症（HCSMA）是一种 显性遗传性下运动神经元疾病，会导致虚弱， 肌肉萎缩和瘫痪从临床和病理上看， 婴儿和儿童的脊髓肌肉萎缩。 以前的研究 集中在脊髓和近端的病理变化， 腹根，并没有提供令人满意的形态学基础 因为受影响的人有着深刻的弱点。 最近 电生理和形态学研究的个人纯合子 提示临床缺陷可能与异常 运动轴突远端部分的传导或变性，或 运动神经末梢ACh释放不足或可能涉及 肌肉本身，尚未系统评估的可能性 迄今 其中几种机制被认为发挥了作用 脊髓灰质炎后综合征的研究 拟议的研究将使用细胞内 记录和刺激技术，以进一步表征 和运动单位功能缺陷的部位。 补充形态学研究将使用免疫细胞化学和 超微结构的方法来确定时间的演变， 神经肌肉接头、远端轴突和 并与电生理数据进行比较 同样的动物。 HCSMA模式提供了一个独特的机会， 在疾病早期调查遗传性运动神经元疾病， 运动神经元功能障碍，但可行的，而次要现象 不要掩盖主要缺陷。

DESCRIPTION: (Adapted from applicant's abstract) Human motor neuron diseases include hereditary spinal muscular atrophies of infants and children, and in adults, amyotrophic lateral sclerosis and the postpolio syndrome. Hereditary Canine Spinal Muscular Atrophy (HCSMA) is a dominantly inherited lower motor neuron disease which produces weakness, muscle atrophy, and paralysis. Clinically and pathologically it resembles the spinal muscular atrophies of infancy and childhood. Previous studies have focused on the pathologic changes in the spinal cord and proximal ventral roots and have not provided a satisfactory morphological basis for the profound weakness in affected individuals. Recent electrophysiological and morphological studies of individuals homozygous for HCSMA suggest that the clinical deficits may be related to abnormal conduction or degeneration in the distal portion of the motor axon or insufficient release of ACh at motor terminals or perhaps involvement of muscle itself, possibilities which have not been evaluated systematically to date. Several of these mechanisms have been suggested to play a role in the postpolio syndrome. The proposed studies will use intracellular recording and stimulation techniques to characterize further the nature and site of motor unit function deficits as the clinical course evolves. Complementary morphologic studies will use immunocytochemical and ultrastructural methods to determine the temporal evolution of the pathologic changes in the neuromuscular junction, distal axons, and skeletal muscle and compare them with electrophysiological data obtained on the same animals. The HCSMA model provides a unique opportunity to investigate an inherited motoneuron disease early in the disease while motoneurons are dysfunctional but viable and while secondary phenomena do not obscure the primary deficits.