Increased oxidative damage to DNA in an animal model of amyotrophic lateral sclerosis.

Substantial evidence suggest that oxidative damage may play a role in the pathogenesis of Amyotrophic Lateral Sclerosis (ALS). We examined levels of 8-Hydroxy-2'-deoxyguanosine (8OH2'dG) in the nuclear DNA from the spinal cord, frontal cortex, striatum and cerebellum from G93A mice at 60, 90, and 120 days of age. We also used in vivo microdialysis to measure free levels of 8OH2'dG and 8-Hydroxyguanine (8OHG) at the same time points in the frontal cortex of G93A mice. Increased 8OH2'dG DNA levels were observed in the spinal cord (at 60, 90 and 120 days), in the cortex (at 90, and 120 days), and in the striatum (at 120 days), as compared to age-matched littermate controls. No significant changes were found in the cerebellum at any of the time points studied. Free levels of 8OH2'dG in the cortex of G93A mice were increased, as compared to control mice, at 90 and 120 days. Free levels of 8OHG were found to be significantly higher at 120 days of age in control mice than in G93A mice. These results provide evidence that in this model of ALS oixidative DNA-damage is increased and base excision-repair may be deficient.