Chronic vitamin C deficiency does not accelerate oxidative stress in ageing brains of guinea pigs.
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.
Section of Biomedicine, Department of Disease Biology, Faculty of Life Sciences, University of Copenhagen, Copenhagen, Denmark.
Pernille
P
Tveden-Nyborg
Stine
S
Hasselholt
Namiyo
N
Miyashita
Torben
T
Moos
Henrik E
HE
Poulsen
Jens
J
Lykkesfeldt
D000367:Age Factors; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001206:Ascorbic Acid Deficiency / Q000134:cerebrospinal fluid / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002908:Chronic Disease; D005260:Female; D005786:Gene Expression Regulation; D005978:Glutathione / Q000378:metabolism; D006168:Guinea Pigs; D006706:Homeostasis; D015227:Lipid Peroxidation; D008099:Liver / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D005978:Glutathione