Malaspina Andrea, Jokic Natasa, Huang Wenlong L, Priestley John V
Neuroscience Centre, Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, Whitechapel, London E1 2AT, UK.
BMC Genomics. 2008 Oct 23;9:500. doi: 10.1186/1471-2164-9-500.
Mutations of the superoxide dismutase 1 (SOD1) gene are linked to amyotrophic lateral sclerosis (ALS), an invariably fatal neurological condition involving cortico-spinal degeneration. Mechanical injury can also determine spinal cord degeneration and act as a risk factor for the development of ALS.
We have performed a comparative ontological analysis of the gene expression profiles of thoracic cord samples from rats carrying the G93A SOD1 gene mutation and from wild-type littermates subjected to mechanical compression of the spinal cord. Common molecular responses and gene expression changes unique to each experimental paradigm were evaluated against the functional development of each animal model. Gene Ontology categories crucial to protein folding, extracellular matrix and axonal formation underwent early activation in both experimental paradigms, but decreased significantly in the spinal cord from animals recovering from injury after 7 days and from the G93A SOD1 mutant rats at end-stage disease. Functional improvement after compression coincided with a massive up-regulation of growth-promoting gene categories including factors involved in angiogenesis and transcription, overcoming the more transitory surge of pro-apoptotic components and cell-cycle genes. The cord from G93A SOD1 mutants showed persistent over-expression of apoptotic and stress molecules with fewer neurorestorative signals, while functional deterioration was ongoing.
this study illustrates how cytoskeletal protein metabolism is central to trauma and genetically-induced spinal cord degeneration and elucidates the main molecular events accompanying functional recovery or decline in two different animal models of spinal cord degeneration.
超氧化物歧化酶1（SOD1）基因突变与肌萎缩侧索硬化症（ALS）相关，ALS是一种涉及皮质脊髓变性的致命性神经疾病。机械损伤也可导致脊髓变性，并作为ALS发病的危险因素。
我们对携带G93A SOD1基因突变的大鼠和遭受脊髓机械压迫的野生型同窝仔鼠的胸段脊髓样本的基因表达谱进行了比较本体分析。针对每个动物模型的功能发展，评估了每个实验范式特有的共同分子反应和基因表达变化。对蛋白质折叠、细胞外基质和轴突形成至关重要的基因本体类别在两种实验范式中均早期激活，但在损伤后7天恢复的动物以及终末期疾病的G93A SOD1突变大鼠的脊髓中显著下降。压迫后功能改善与促进生长的基因类别大量上调同时发生，这些基因类别包括参与血管生成和转录的因子，克服了促凋亡成分和细胞周期基因的短暂激增。G93A SOD1突变体的脊髓显示凋亡和应激分子持续过度表达，神经修复信号较少，而功能恶化仍在进行。
本研究阐明了细胞骨架蛋白代谢如何在创伤和基因诱导的脊髓变性中起核心作用，并阐明了两种不同脊髓变性动物模型中伴随功能恢复或衰退的主要分子事件。
