Increased formation of reactive oxygen species, but no changes in glutathione peroxidase activity, in striata of mice transgenic for the Huntington's disease mutation

The formation of reactive oxygen species (ROS) and the activities of the antioxidant enzymes glutathione peroxidase (GPx) and catalase (CAT) were measured as a function of age in the striatum of mice transgenic for the Huntington's disease (HD) mutation. Striata from R6/1 transgenic male mice were dissected at different ages (11, 19, and 35 weeks). The amount of dichlorofluorescein (DCF), an index of ROS formation, was significantly increased in R6/1 mice at all ages tested, whereas GPx activity remained unchanged when compared with wild-type control animals in all groups evaluated. CAT activity was very low, just above detection in the striata of both control and transgenic mice. Nineteen and 35-week-old R6/1 mice also developed feet clasping behavior, but only 35-week-old animals showed body weight loss. Our findings support an active role of free radicals in the onset and progression of the neurological phenotype of R6/1 mice. We suggest that changes in ROS formation are due to an age-related increased propensity of the striatum of transgenic animals to generate oxygen radicals as a response to the evolving pathological conditions.