Vitamin C deficiency increases basal exploratory activity but decreases scopolamine-induced activity in APP/PSEN1 transgenic mice.
Vitamin C deficiency increases basal exploratory activity but decreases scopolamine-induced activity in APP/PSEN1 transgenic mice.
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DOI：
10.1016/j.pbb.2009.11.009
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发表时间：
2010-02
影响因子：
3.6
通讯作者：
McDonald, M. P.
中科院分区：
文献类型：
--
作者：
Harrison, F. E.;May, J. M.;McDonald, M. P.
关键词：
维生素C是一种强大的抗氧化剂，阿尔茨海默氏症患者的维生素C水平会降低。即使是亚临床维生素C缺乏症也会影响疾病的发展。为了探讨这一原理，我们将APP/PSEN1转基因小鼠与无法合成自身维生素C的Gulo基因敲除小鼠杂交，从6周龄开始维持标准水平(0.33g/L)或降低(0.099 g/L)维生素C水平，然后评估行为和神经病理学的变化。APP/PSEN1小鼠在Barnes迷宫和水迷宫中表现出空间学习障碍，而不受维生素C水平的进一步影响。然而，长期降低维生素C水平导致转基因小鼠活动过度，运动习惯改变，巴恩斯迷宫中遗漏错误增加。维生素C的减少也会导致氧化应激增加。转基因小鼠更容易受到东莨菪碱的活性增强作用的影响，而低维生素C在两种基因型中都会减弱这些作用。这些数据表明，胆碱能系统和维生素C之间的相互作用可能是重要的，因为胆碱能退化与阿尔茨海默病相关。
Vitamin C is a powerful antioxidant and its levels are decreased in Alzheimer's patients. Even sub-clinical vitamin C deficiency could impact disease development. To investigate this principle we crossed APP/PSEN1 transgenic mice with Gulo knockout mice unable to synthesize their own vitamin C. Experimental mice were maintained from 6 weeks of age on standard (0.33 g/L) or reduced (0.099 g/L) levels of vitamin C and then assessed for changes in behavior and neuropathology. APP/PSEN1 mice showed impaired spatial learning in the Barnes maze and water maze that was not further impacted by vitamin C level. However, long-term decreased vitamin C levels led to hyperactivity in transgenic mice, with altered locomotor habituation and increased omission errors in the Barnes maze. Decreased vitamin C also led to increased oxidative stress. Transgenic mice were more susceptible to the activity-enhancing effects of scopolamine and low vitamin C attenuated these effects in both genotypes. These data indicate an interaction between the cholinergic system and vitamin C that could be important given the cholinergic degeneration associated with Alzheimer's disease.
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影响因子：
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