Comparative gene expression analysis of thoracic spinal cord from G93A SOD1 mutant rats and from wild type littermates following mild compression injury

In this study we investigate how the molecular response to a mechanical stress applied to the spinal cord can be modified by a G93A SOD1 gene mutation, a genetic defect known to cause an invariably fatal form of motor neuron disease. In a 7-day post-injury time period, we perform a 4 time points gene expression profiling of injured spinal cords obtained from pre-symptomatic rats over-expressing the G93A SOD1 gene mutation and from wild type (WT) littermates. The hypothesis tested in this investigation is that the presence of a known genetic defect in a pre-symptomatic rat with a macroscopically normal spinal cord modifies the molecular response to mechanical stress as part of an increase genetically-induced vulnerability to this kind of stress. A better understanding of the molecular mechanisms underlying this susceptibility to trauma may open the way to the uncovering of molecular events which are crucially linked to neurodegenerastion.本研究旨在探究：G93A超氧化物歧化酶1（G93A SOD1）基因突变可如何改变脊髓对机械应激的分子应答反应——该基因突变是一种已知的、会引发致命性运动神经元疾病的遗传缺陷。本研究在损伤后7天的时间窗内，设置4个时间点，对过表达G93A SOD1基因突变的症状前大鼠，以及同窝野生型（WT）对照大鼠的损伤脊髓组织开展基因表达谱分析。本研究验证的假说为：在脊髓宏观外观正常的症状前大鼠体内，已知遗传缺陷的存在会改变其对机械应激的分子应答反应，这一改变本质上是该类应激的遗传诱导易感性升高的体现。深入阐明此类创伤易感性背后的分子机制，或可为揭示与神经退行性变密切相关的分子事件开辟新的研究路径。