Chronic Vitamin C Deficiency does not Accelerate Oxidative Stress in Ageing Brains of Guinea Pigs

Abstract

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.The overall prevalence of age-associated brain disorders such as Alzheimer's disease, Parkinsonism and dementia is increasing in the Western World as a natural consequence of the improved average lifetime expectancy [1][2][3]. This has prompted investigations into the underlying mechanisms associated with ageing to become a growing field of interest. One of the areas receiving particular attention and subject to debate is the putative relationship between oxidative stress, the intake of different nutritional factors -such as antioxidantsand the development and prevention of age-related disorders [4]. Increases in cellular reactive oxygen species (ROS) has consistently been reported during ageing [5]. The increase in ROS is reflected by a decreased gene transcription resulting in cellular stress and oxidative DNA damage -as seen in the brain [6] -and oxidative mitochondrial damage followed by mitochondrial dysfunction [7,8]. Furthermore, DNA repair mechanisms are reduced adding further to the harmful consequences of the oxidative damage in the cell [9].In the brain, vitamin C (ascorbate/ASC) plays a pivotal role in maintaining redox homoeostasis and has additional functions, that is, reducing the risk of neuronal damage because of excess dopamine and glutamate...

Chronic Vitamin C Deficiency Promotes Redox Imbalance in the Brain but Does Not Alter Sodium-Dependent Vitamin C Transporter 2 Expression

“…A study with Svct2 +/− mice compared to wild type demonstrated that VitC levels in brain cortex were genotype dependent with higher VitC content in mice homozygous for Svct2 (+/+) compared to heterozygous counterparts [18], supporting the SVCT2 as the predominant active transporter to the brain. This is in agreement with findings of undetectable mRNA levels of SVCT1 (which is present in other organs, e.g., the liver) in guinea pig brain homogenate [19] Within the brain differential VitC retention in specific brain regions has been reported [20]. Dietary intervention studies have shown increases in Svct2 mRNA expression in the liver, both in vitro and in vivo , but not in the brain following VitC deficiency in mice unable to synthesize VitC ( Gulo −/− ) [21,22].…”

Effects of Ascorbic Acid Deficiency on Protein and Lipid Oxidation in Livers from SMP30/GNL Knockout Mice

“…That outcome is consistent with our results in the mouse liver. Moreover, since Tveden-Nyborg et al reported that a chronic AA deficiency did not change lipid oxidation levels in livers from guinea pigs (41), an AA deficiency may specifically affect the oxidation of proteins but not lipids in the liver. Tanaka et al described the interactions between AA and vitamin E after using ODS rats fed an AA-free and vitamin E-free diet (42).…”

Does Vitamin C Deficiency Affect Cognitive Development and Function?

“…Notably, as both rat and mouse models are capable of synthesizing VitC, results should be interpreted with caution as the findings may not translate well to humans. In aging guinea pigs subjected to long term, non-scorbutic VitC deficiency (100 mg VitC/kg feed), no significant effects of age on biochemical markers in the brain were detected compared to controls (323 mg VitC/kg feed), and it was concluded that the age-related change in VitC status observed in several species is more likely related to maturation rather than aging per se [115,116]. …”