Effect of alpha-lipoic acid on memory, oxidation, and lifespan in SAMP8 mice.

Oxidative damage is associated with neurodegenerative disorders such as Alzheimer's disease (AD). The antioxidant alpha-lipoic acid has been found to improve memory in mouse models of AD. Here, we administered alpha-lipoic acid daily to SAMP8 mice starting at 11 months of age and continuing until death. We found that treatment with alpha-lipoic acid decreased survival from 34 weeks in those receiving vehicle to 20 weeks. A subset of 18 month old mice given alpha-lipoic acid for two weeks and then tested in an object-place recognition paradigm had improved memory. A second subset of 18 month old mice given alpha-lipoic acid for two weeks and tested in the Barnes maze had improved learning. After testing, the mice were sacrificed and indices of oxidative damage were measured in the brain tissue. The mice that received alpha-lipoic acid had significantly increased glutathione and decreased glutathione peroxidase and malondialdehyde indicating reversal of oxidative stress. These results indicate that alpha-lipoic acid improves memory and reverses indices of oxidative stress in extremely old SAMP8 mice, but decreases lifespan. These findings are similar to studies using other types of antioxidants.