Elevated oxidative stress and sensorimotor deficits but normal cognition in mice that cannot synthesize ascorbic acid
Article first published online: 7 MAY 2008
© 2008 The Authors. Journal Compilation © 2008 International Society for Neurochemistry
Journal of Neurochemistry
Volume 106, Issue 3, pages 1198–1208, August 2008
How to Cite
Harrison, F. E., Yu, S. S., Van Den Bossche, K. L., Li, L., May, J. M. and McDonald, M. P. (2008), Elevated oxidative stress and sensorimotor deficits but normal cognition in mice that cannot synthesize ascorbic acid. Journal of Neurochemistry, 106: 1198–1208. doi: 10.1111/j.1471-4159.2008.05469.x
- Issue published online: 15 JUL 2008
- Article first published online: 7 MAY 2008
- Received January 21, 2008; revised manuscript received April 21, 2008; accepted April 27, 2008.
- Alzheimer’s disease;
- ascorbic acid;
- motor deficits;
- oxidative stress
Oxidative stress is implicated in the cognitive deterioration associated with normal aging as well as neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. We investigated the effect of ascorbic acid (vitamin C) on oxidative stress, cognition, and motor abilities in mice null for gulono-γ-lactone oxidase (Gulo). Gulo−/− mice are unable to synthesize ascorbic acid and depend on dietary ascorbic acid for survival. Gulo−/− mice were given supplements that provided them either with ascorbic acid levels equal to- or slightly higher than wild-type mice (Gulo-sufficient), or lower than physiological levels (Gulo-low) that were just enough to prevent scurvy. Ascorbic acid is a major anti-oxidant in mice and any reduction in ascorbic acid level is therefore likely to result in increased oxidative stress. Ascorbic acid levels in the brain and liver were higher in Gulo-sufficient mice than in Gulo-low mice. F4-neuroprostanes were elevated in cortex and cerebellum in Gulo-low mice and in the cortex of Gulo-sufficient mice. All Gulo−/− mice were cognitively normal but had a strength and agility deficit that was worse in Gulo-low mice. This suggests that low levels of ascorbic acid and elevated oxidative stress as measured by F4-neuroprostanes alone are insufficient to impair memory in the knockouts but may be responsible for the exacerbated motor deficits in Gulo-low mice, and ascorbic acid may have a vital role in maintaining motor abilities.