MOTOR NEURON DISEASE--NEUROPHYSIOLOGY AND PATHOLOGY

描述：(摘自申请者的摘要)人类运动神经元 疾病包括遗传性婴儿脊肌萎缩和 儿童和成人的肌萎缩侧索硬化症和脊髓灰质炎后 综合症。遗传性犬脊髓肌萎缩症(HCSMA)是一种 主要遗传的是会导致虚弱的下层运动神经元疾病， 肌肉萎缩和瘫痪。从临床和病理上看，它类似于 婴儿期和儿童期的脊髓性肌肉萎缩。以前的研究 都专注于脊髓和近端的病理变化 腹根，没有提供令人满意的形态基础 对受影响个人的严重虚弱负责。近期 纯合子个体的电生理和形态研究 对于HCSMA提示临床缺陷可能与异常有关 运动轴突远端的传导或变性 运动终末ACh释放不足或可能参与 肌肉本身，还没有系统地评估过的可能性 到目前为止。其中有几种机制被认为发挥了作用 在小儿麻痹症后综合症中。拟议的研究将使用细胞内 记录和刺激技术，以进一步表征自然 随着临床病程的进展，运动单位功能缺陷的部位也逐渐增多。 补充形态研究将使用免疫细胞化学和 用超微结构方法确定血管内皮细胞的时间演化 神经肌肉接头、远端轴突和 并将其与获得的电生理数据进行比较 在相同的动物身上。HCSMA模式提供了一个独特的机会 在疾病的早期调查遗传性运动神经元疾病 运动神经元功能障碍，但仍可存活，而且是次要现象 不要掩盖主要赤字。

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.