DOXORUBICIN-INDUCED MOTOR NEURON AND SCHWANN CELL DEATH

阿霉素（阿霉素）是一种自身荧光蒽环类抗生素 作用于细胞核的抗生素， 插入DNA的碱基对之间，从而抑制DNA- 指导信使RNA合成。 神经内微量注射 0.19-0.38微克阿霉素导致延迟选择性施万氏反应 细胞变性和伴随的脱髓鞘， 严重影响轴突 当大于或 相当于0.5微克的阿霉素被注射，它也是逆行性的， 运输到前角细胞， 这些低级运动神经元的退化。 我们计划研究这两个实验上可分离的过程， 更多细节 使用电生理和 神经病理学方法，我们计划进一步研究阿霉素- 诱导的运动神经元变性作为可能的模型， 肌萎缩侧索硬化症（ALS）。 我们将确定， 轴突长度、轴突直径和神经元的特征， 功能与神经元脆弱性相关。 使用免疫- 我们计划用组织化学方法来鉴定卫星细胞 其在多柔比星的细胞间转移后被标记 来自前角细胞。 此外，可能存在跨细胞的 这种毒素转运到中间神经元和上运动神经元 突出到前角。 这个新的动物模型 毒素诱导的运动退化可能为 人类运动神经元变性的病因，特别是 人症 此外，细胞间的神经毒性可能是 其他神经系统发病的重要线索 疾病 在一组单独的观察中，我们计划进一步描述一些 多柔比星诱导的 周围神经雪旺细胞变性/脱髓鞘。 使用针对Na+的组成部分产生的抗体， 通道，我们将确定Na+通道沿着的分布 脱髓鞘和髓鞘再生轴突。 将这些 免疫细胞化学结果和电生理数据 应提供资料，说明 脱髓鞘的轴突重新建立传导。 这些研究是 对于理解病理生理学 发生在人类脱髓鞘疾病中的变化。

Doxorubicin (Adriamycin) is an autofluorescent anthracycline antineoplastic antibiotic that acts at the cell nucleus by intercalating between base pairs of DNA thus inhibiting DNA- directed messenger RNA synthesis. Intraneural microinjection of 0.19-0.38 mug of doxorubicin causes a delayed selective Schwann cell degeneration and accompanying demyelination without significantly affecting axons. However when greater than or equal to 0.5 mug of doxorubicin is injected, it is also retrogradely transported to anterior horn cells causing a delayed progressive degeneration of these lower motor neurons. We plan to study these two experimentally separable processes in greater detail. Using both electrophysiological and neuropathological methods we plan to further study doxorubicin- induced motor neuron degeneration as as possible model of amyotrophic lateral sclerosis (ALS). We will determine if such characteristics as axonal length, axonal diameter, and neuronal function correlate with neuron vulnerability. Using immuno- histochemical methods we plan to identify the satellite cells which are labeled following intercellular transfer of doxorubicin from anterior horn cells. In addition, there may be transcellular transport of this toxin to interneurons and upper motor neurons projecting to the anterior horn. This new animal model of a toxin-induced motor degeneration may provide new insights into the etiology of human motor neuron degenerations, especially ALS. additionally the intercellular of neurotoxicity could be an important clue to the pathogenesis of other nervous system diseases. In a separate set of observations we plan to further describe some of the pathophysiological consequences of doxorubicin-induced Schwann cell degeneration/demyelination in peripheral nerve. Using antibodies generated against component parts of the Na+ channel, we will determine the Na+ channel distribution along demyelinated and remyelinating axons. Correlating these immunocytochemical findings with electrophysiological data should provide information concerning the mechanism by which demyelinated axons re-establish conduction. These studies are of obvious importance for understanding the pathophysiological changes that occur in human demyelinating diseases.