Increased oxidative damage to DNA in an animal model of amyotrophic lateral sclerosis
Increased oxidative damage to DNA in an animal model of amyotrophic lateral sclerosis
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DOI：
10.1080/10715760400027979
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发表时间：
2005-04-01
影响因子：
3.3
通讯作者：
Bogdanov, MB
中科院分区：
文献类型：
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作者：
Aguirre, N;Beal, MF;Bogdanov, MB
大量证据表明，氧化损伤可能在肌萎缩侧索硬化症（ALS）的发病机制中发挥作用。我们检测了60、90和120日龄G93 A小鼠的脊髓、额叶皮质、纹状体和小脑的核DNA中8-羟基-2 '-脱氧鸟苷（8 OH 2'dG）的水平。我们还使用体内微透析来测量G93 A小鼠额叶皮层中相同时间点的80 H2 'dG和8-羟基鸟嘌呤（80 HG）的游离水平。与年龄匹配的同窝对照相比，在脊髓（在60、90和120天）、皮质（在90和120天）和纹状体（在120天）中观察到增加的80 H2 'dG DNA水平。在研究的任何时间点，小脑均未发现显着变化。与对照小鼠相比，在90和120天时，G93 A小鼠皮质中的80 H2 'dG的游离水平增加。发现对照小鼠在120日龄时的8 OHG游离水平显著高于G93 A小鼠。这些结果提供了证据表明，在ALS的这种模型中，氧化性DNA损伤增加，并且碱基切除修复可能是缺陷的。
Substantial evidence suggest that oxidative damage may play a role in the pathogenesis of Amyotrophic Lateral Sclerosis (ALS). We examined levels of 8-Hydroxy-2'-deoxyguanosine (8OH2'dG) in the nuclear DNA from the spinal cord, frontal cortex, striatum and cerebellum from G93A mice at 60, 90, and 120 days of age. We also used in vivo microdialysis to measure free levels of 8OH2'dG and 8-Hydroxyguanine (8OHG) at the same time points in the frontal cortex of G93A mice. Increased 8OH2'dG DNA levels were observed in the spinal cord (at 60, 90 and 120 days), in the cortex (at 90, and 120 days), and in the striatum (at 120 days), as compared to age-matched littermate controls. No significant changes were found in the cerebellum at any of the time points studied. Free levels of 8OH2'dG in the cortex of G93A mice were increased, as compared to control mice, at 90 and 120 days. Free levels of 8OHG were found to be significantly higher at 120 days of age in control mice than in G93A mice. These results provide evidence that in this model of ALS oixidative DNA-damage is increased and base excision-repair may be deficient.