Elevated oxidative stress in the brain of senescence-accelerated mice at 5 months of age
Elevated oxidative stress in the brain of senescence-accelerated mice at 5 months of age
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DOI：
10.1007/s10522-005-6041-2
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发表时间：
2006-02-01
期刊：
影响因子：
4.5
通讯作者：
Coto-Montes, A
中科院分区：
文献类型：
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作者：
Alvarez-García, O;Vega-Naredo, I;Coto-Montes, A
加速衰老小鼠（senescence-accelerated mouse，SAM）是研究衰老或年龄相关疾病的理想动物模型。在本研究中，我们使用了多学科的方法来表征发生在衰老和大脑衰老的建模中的变化。5月龄的SAMP 8小鼠表现出神经胶质增生和分子氧化损伤的增加。同样，我们发现，超氧化物歧化酶活性下降，而过氧化氢酶和谷胱甘肽还原酶的活性没有差异。这些结果表明，超氧化物歧化酶的减少可能参与了SAMP 8在幼年期脑组织中氧化应激的增加。这一建议得到了α-突触核蛋白和磷酸化tau蛋白表达增加的支持，这与抗氧化酶的下降同时发生。α-突触核蛋白聚集体总是与tau病理学相关，我们的结果表明，α-突触核蛋白积累不仅在神经退行性疾病中，而且在正常衰老中是tau病理学的有效诱导物。这些结果还意味着SAMP 8从早期就暴露于高水平的氧化应激，这可能是该菌株中所见的大脑衰老相关损伤和退化的一个非常重要的原因。
The senescence-accelerated mouse (SAM) is a useful animal model to study aging or age-associated disorder. In the present study, we have used a multidisciplinary approach to the characterization of changes that occur in aging and in the modelling of brain aging. The SAMP8 mouse at 5 months of age exhibited an increase in gliosis and molecular oxidative damage. Likewise, we found that superoxide dismutase activity decreased compared with age-matched SAMR1 while there were no differences in activity of catalase and glutathione reductase. These results indicate that the decrease of superoxide dismutase may be involved in the increase of oxidative stress in brain of SAMP8 at younger stages. This suggestion is supported by an increase in the expression of alpha-synuclein together with phosphorylated tau protein, which is concurrent with the decline of that antioxidant enzyme. Alpha-synuclein aggregates are invariably associated with tau pathologies and our results demonstrate that alpha-synuclein accumulation is a potent inducer of tau pathologies not only in neurodegenerative diseases but also in normal aging. These results also imply that SAMP8 are exposed to elevated levels of oxidative stress from an early age, and that could be a very important cause of the senescence-related impairments and degeneration in the brain seen in this strain.