Section of Biomedicine, Department of Disease Biology, Faculty of Life Sciences, University of Copenhagen, Copenhagen, Denmark.
Basic Clin Pharmacol Toxicol. 2012 Jun;110(6):524-9. doi: 10.1111/j.1742-7843.2011.00852.x. Epub 2012 Jan 20.
Increased oxidative stress in the brain has consistently been implied in ageing and in several degenerative brain disorders. Acting as a pivotal antioxidant in the brain, vitamin C is preferentially retained during deficiency and may play an essential role in neuroprotection during ageing. Thus, a lack of vitamin C could be associated with an increase in redox imbalance in the ageing brain. The present study compared oxidative stress of ageing to that of a long-term non-scorbutic vitamin C deficiency in guinea pigs. Adults (3-9 months old) were compared to old (36-42 months old) animals during a 6-month dietary intervention by assessing vitamin C transport and redox homoeostasis in the brain. In contrast to our hypothesis, chronic vitamin C deficiency did not affect the measured markers of oxidative stress in the brains of adult and aged animals. However, aged animals generally showed increased lipid oxidation (p < 0.001), decreased glutathione (p < 0.05), increased p53 mRNA expression (p < 0.01) and somewhat elevated DNA oxidation (p = 0.08) compared to adult counterparts irrespective of dietary vitamin C intake. Increased mRNA expression of sod1 (p < 0.05) and svct2 (p = 0.05) was observed in aged animals together with increased superoxide dismutase activity (p < 0.01) and cerebrospinal fluid vitamin C status (p < 0.001) suggesting a compensatory effort that did not counterbalance the effects of ageing. Essentially, no effects of age were observed in the liver demonstrating the brain's unique susceptibility to redox imbalance. Consistent with previous findings, we show that ageing per se constitutes a considerable oxidative insult in the brain. However, our data also suggest that a long-term poor vitamin C status does not accelerate this process.
大脑中的氧化应激增加一直与衰老和几种退行性脑疾病有关。维生素 C 作为大脑中的主要抗氧化剂，在缺乏时优先保留，并且在衰老过程中可能发挥重要的神经保护作用。因此，维生素 C 的缺乏可能与衰老大脑中氧化还原失衡的增加有关。本研究比较了衰老和长期非坏血病性维生素 C 缺乏症对豚鼠大脑的氧化应激的影响。通过评估大脑中维生素 C 的转运和氧化还原稳态，将成年（3-9 个月）与老年（36-42 个月）动物在 6 个月的饮食干预中进行比较。与我们的假设相反，慢性维生素 C 缺乏症并没有影响成年和老年动物大脑中测量的氧化应激标志物。然而，与成年动物相比，老年动物的脂质氧化普遍增加（p<0.001），谷胱甘肽减少（p<0.05），p53mRNA 表达增加（p<0.01），DNA 氧化稍微升高（p=0.08），无论饮食中维生素 C 的摄入量如何。老年动物的 sod1mRNA 表达增加（p<0.05）和 svct2mRNA 表达增加（p=0.05），同时超氧化物歧化酶活性增加（p<0.01）和脑脊液维生素 C 状态增加（p<0.001），表明一种代偿性的努力，但未能抵消衰老的影响。本质上，肝脏中没有观察到年龄的影响，这表明大脑对氧化还原失衡的独特敏感性。与先前的研究结果一致，我们表明衰老本身就是大脑中的一个相当大的氧化损伤。然而，我们的数据还表明，长期缺乏维生素 C 状态不会加速这一过程。
