SELECTIVE NEURONAL INVOLVEMENT IN MOTOR NEURON DISEASE

某些运动神经元受到严重影响的原因是运动神经元 疾病，如肌萎缩性侧索硬化症（ALS），而其他疾病， 幸免于难，完全未知。 目前在这方面的知识存在很大差距 需要填补这一问题，因为基本机制可能与 运动神经元变性的发病机制。 我们有机会 通过使用摇摆鼠来研究这一机制，摇摆鼠是一种 遗传性运动神经元病 这种运动神经元疾病的本质 被广泛研究，并被认为是一个有价值的模型， 运动神经元疾病过程的研究。 摇摆鼠 表现出选择性神经元受累的独特特征： 运动神经元受到影响，但腰部运动神经元不受影响。 尽管 这种运动神经元疾病的病理过程是一种 原发性神经元病，轴突再生发生在响应于两者 自发性轴突变性和轴突切断。 轴突再生可能是 运动神经元退化的关键补偿过程。 我们的目标是，通过 将摇摆小鼠与其正常同窝出生的小鼠进行比较，以：（1）确定 两组运动神经元的差异是否是由于 不同的再生能力;（2）确定这种差异是否 基于RNA和/或蛋白质合成的差异;（3）确定是否 再生能力的差异是基于 轴突运输;（4）确定再生的差异是否 容量基于慢轴突运输的差异。 轴突 将应用传输技术定量分析轴突 再生后的神经挤压和量化的数量和速度的快速 轴索切断前后轴突运输均缓慢。 变化 将通过以下方法研究多肽组成： 聚丙烯酰胺凝胶电泳和荧光照相。 逆行 轴突运输技术，再生所需的时间间隔 将确定到达肌肉的轴突。 神经元RNA和蛋白质 通过定量放射自显影术测量合成。 该分析 神经元功能在两个不同的影响运动神经元和 健康动物的运动神经元群最终会导致 对运动神经元变性机制的新认识。 是 合理地预期，我们的知识最终将导致进一步的 研究促进或保护的药理学方法 受运动神经元疾病影响的运动神经元的修复机制， 如ALS。

The reason why certain motor neurons are severely affected in motor neuron disease, such as amyotrophic lateral sclerosis (ALS), while others are spared, is entirely unknown. A large gap in the current knowledge on this issue needs to be filled, since the underlying mechanism may relate to the pathogenesis of motor neuron degeneration. We have an opportunity to investigate this mechanism by using the wobbler mouse, an animal with hereditary motor neuron disease. The nature of this motor neuron disease has been extensively studied and considered a valuable model for the investigation of motor neuron disease processes. The wobbler mouse presents with unique features of selective neuronal involvement: cervical motor neurons are affected but lumbar motor neurons are spared. Despite the fact that the pathological process of this motor neuron disease is a primary neuronopathy, axonal regeneration occurs in response to both spontaneous axonal degeneration and axotomy. Axonal regeneration may be a key process for compensating against motor neuron degeneration. We aim, by comparing wobbler mice to their normal littermates, to: (1) determine whether the difference in the two groups of motor neurons is due to different regenerative capacity; (2) determine whether this difference is based on differences in RNA and/or protein synthesis; (3) determine whether the difference in regenerative capacity is based on differences in fast axonal transport; (4) determine whether the difference in regenerative capacity is based on differences in slow axonal transport. Axonal transport techniques will be applied to analyze quantitatively axonal regeneration after nerve crush and to quantify the amount and rate of fast and slow axonal transport both before and after axotomy. Changes in polypeptide composition will be studied by polyacrylamide-gel-electrophoresis and fluorography. With retrograde axonal transport techniques, the time interval required for regenerating axons to arrive at the muscle will be determined. Neuronal RNA and protein synthesis will be measured by quantitative autoradiography. This analysis of neuronal functions in both differently affected motor neurons and the same groups of motor neurons in healthy animals will ultimately lead to a new understanding of mechanisms of motor neuron degeneration. It is reasonable to anticipate that our knowledge will eventually lead to further investigation on pharmacological methods for facilitating or protecting the reparative mechanism in motor neurons affected by motor neuron disease, such as ALS.