Gene Expression in Motor Neurons with Differential Susceptibility to ALS

运动神经元死亡是肌萎缩侧索硬化症（ALS）的主要特征， 导致瘫痪和死亡的神经退行性疾病。虽然大多数运动神经元死亡 在肌萎缩侧索硬化症中，一些人群对退化有抵抗力。这一探索性建议旨在 比较对ALS有抵抗力的运动神经元和 易患ALS这些实验的长期目标是确定基因， 保护某些运动神经元，并最终诱导这些基因的表达 在运动神经元中的作用。为了实现这些目标，我们将比较 球海绵体肌和眼神经核中的基因表达， 对ALS有抵抗力，基因表达在背外侧后核和三叉神经核，运动神经核， 在野生型和ALS转基因大鼠中，对ALS易感的神经元群体。的 具体目标1：比较不同群体中的基因表达， 运动神经元对肌萎缩侧索硬化症的易感性不同。这些实验将使用基因 激光捕获显微切割和RNA扩增后运动神经元的微阵列分析。 具体目标2：检查运动神经元中鉴定的特定基因的表达， 对ALS的不同易感性。这些实验将使用RT-PCR、原位杂交和 免疫组化具体目标3：确定是否与ALS相关的分子- 抗运动神经元在ALS转基因大鼠模型中受到不同的影响。这些 实验将使用特异性目标2技术在转基因SOD-1突变大鼠中进行。 运动神经元的死亡是ALS的一个标志，ALS是一种致命的麻痹性神经疾病。 了解一些运动神经元群体如何抵抗退化，即使是在晚期 疾病，可能提供有关运动神经元基因治疗靶点的线索， ALS的退化

Motor neuron death is a major feature of amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease that leads to paralysis and death. Although most motor neurons die in ALS, some populations are resistant to degeneration. This exploratory proposal is designed to compare gene expression in motor neurons that are resistant to ALS with those that are vulnerable to ALS. The long term objectives of these experiments are to identify genes that confer protection to certain motor neurons and, ultimately, to induce expression of these genes in motor neurons that typically succumb to ALS. To accomplish these goals, we will compare gene expression in the bulbocavernosus and oculomotor nuclei, motor neuron populations that are resistant to ALS, with gene expression in the retrodorsolateral and trigeminal nuclei, motor neuron populations that are vulnerable to ALS, in both wildtype and ALS transgenic rats. The following aims will be investigated: Specific Aim 1: Compare gene expression in populations of motor neurons with differential susceptibility to ALS. These experiments will use gene microarray analysis of motor neurons after laser capture microdissection and RNA amplification. Specific Aim 2: Examine expression of specific genes identified in motor neurons with differential susceptibility to ALS. These experiments will use RT-PCR, in situ hybridization and immunohistochemistry. Specific Aim 3: Determine whether molecules associated with ALS- resistant motor neurons are differentially affected in a transgenic rat model of ALS. These experiments will use the techniques of Specific Aim 2 in transgenic SOD-1 mutant rats. Death of motor neurons is a hallmark of ALS, a paralyzing neurological disease that is fatal. Understanding how some motor neuron populations resist degeneration, even in late stage disease, may provide clues about targets for gene therapy in motor neurons at risk for degeneration in ALS.