Reversal of age-related learning deficits and brain oxidative stress in mice with superoxide dismutase/catalase mimetics
Reversal of age-related learning deficits and brain oxidative stress in mice with superoxide dismutase/catalase mimetics
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DOI：
10.1073/pnas.1332809100
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发表时间：
2003-07-08
影响因子：
11.1
通讯作者：
Baudry, M
中科院分区：
文献类型：
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作者：
Liu, RL;Liu, IY;Baudry, M
氧化应激与老年实验动物和老年人类的认知障碍有关。这意味着大脑中的抗氧化防御机制不足以防止与年龄相关的氧化损伤的增加，饮食中摄入各种抗氧化剂可能有利于保护大脑功能。在这里，我们报告了从8个月到11个月大的小鼠学习和记忆功能的戏剧性丧失，与大脑氧化应激的几个标志物显著增加有关。两种合成的催化活性氧清除剂Eukarion实验化合物EUK-189和EUK-207从8个月到11个月的长期全身给药几乎完全逆转了在这段时间内大脑中发生的认知缺陷和氧化应激增加。特别是，蛋白质氧化的增加被完全阻止，而脂质过氧化的增加减少了大约50%。此外，我们观察到背景恐惧学习和大脑中蛋白质氧化水平之间存在显著的负相关。这些结果进一步支持了活性氧在年龄相关学习障碍中的作用，并提示了合成催化活性氧清除剂的潜在临床应用。
Oxidative stress has been implicated in cognitive impairment in both old experimental animals and aged humans. This implication has led to the notion that antioxidant defense mechanisms in the brain are not sufficient to prevent age-related increase in oxidative damage and that dietary intake of a variety of antioxidants might be beneficial for preserving brain function. Here we report a dramatic loss of learning and memory function from 8 to 11 months of age in mice, associated with marked increases in several markers of brain oxidative stress. Chronic systemic administration of two synthetic catalytic scavengers of reactive oxygen species, Eukarion experimental compounds EUK-189 and EUK-207, from 8 to 11 months almost completely reversed cognitive deficits and increase in oxidative stress taking place during this time period in brain. in particular, increase in protein oxidation was completely prevented, whereas increase in lipid peroxidation was decreased by approximate to50%. In addition, we observed a significant negative correlation between contextual fear learning and levels of protein oxidation in brain. These results further support the role of reactive oxygen species in age-related learning impairment and suggest potential clinical applications for synthetic catalytic scavengers of reactive oxygen species.