MOTOR NEURON DISEASE--NEUROPHYSIOLOGY AND PATHOLOGY

遗传性犬脊髓性肌萎缩症（HCSMA）是一种 下运动神经元的显性遗传性疾病， 导致虚弱肌肉萎缩和瘫痪 临床和 在病理学上，HCSMA类似于 婴儿期和儿童期，并与其他 运动单位系统功能的形式在严重受影响的 纯合子HCSMA个体。 我们的研究结果突出了 神经肌肉传递缺陷的重要性， HCSMA出现的弱点，表明， 氨基吡啶类药物可以短暂改善 运动单位功能失调，并提出了可能的作用， 神经元活动本身导致运动单位功能障碍。 我们现在 提出实验，重点放在这些机制背后 缺陷和检查细胞骨架异常如何可能有助于 HCSMA的发病机制。 我们将决定 在两种HCSMA中观察到的近端轴突异常 和人类运动神经元疾病（ALS）与 运动单位功能障碍 我们将在体外使用 从肌纤维记录，活体显微镜和荧光 进一步了解神经传递的染色方法 HCSMA的缺陷以及这些缺陷是否与结构性 神经肌肉接头处的变化。 慢性电 肌肉神经的刺激将被用来检查的作用， 确定运动单位功能障碍的活性。 我们还研究了 神经丝磷酸化水平在多大程度上 随着HCSMA临床弱点的演变。 HCSMA 模型继续提供独特的机会， 运动神经元疾病潜在的可能机制， 评估旨在防止电机损耗的潜在解决方案 单位功能

Hereditary Canine spinal Muscular Atrophy (HCSMA) is a dominantly inherited disorder of lower motor neurons which produces weakness, muscle atrophy, and paralysis. Clinically and pathologically, HCSMA resembles the spinal muscular atrophies of infancy and childhood and shares important features with other forms of motor units sysfunction evolves in severely affected homozygous HCSMA individuals. Our results highlight the importance of neuromuscular transmission deficits in the initial appearance of weakness in HCSMA, demonstrate that aminoopyridine drugs can improve transiently the performance of dysfunctional motor units and suggest a possible role for motor neuron activity itself in causing motor unit dysfunction. We now propose experiments that focus on mechanisms underlying these deficits and examine how cytoskeletal abnormalities may contribute to the pathogenesis of HCSMA. We will determine whether proximal axonal abnormalities that are observed in both HCSMA and human motor neuron disease (ALS) are associated with dysfunctional motor unit performance. We will use in vitro recording from muscle fibers, vital microscopy and fluorescent staining methods to gain further understanding of neurotransmission deficits in HCSMA and whether these are associated with structural changes at the meuromuscular junction. Chronic electrical stimulation of muscle nerves will be used to examine the role of activity in determining motor unit dysfunction. We also examine to what extent neurofilament phosphorylation levels are associated with the evolution of clinical weakness in HCSMA. The HCSMA model continues to provide unique opportunities to investigate possible mechanisms underlying motor neuron diseases and to evaluate potential solutions directed at preventing the loss of motor unit function.