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Increased Formation of Reactive Oxygen Species, but No Changes in Glutathione Peroxidase Activity, in Striata of Mice Transgenic for the Huntington's Disease Mutation

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Abstract

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.

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Correspondence to José Segovia.

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Pérez-Severiano, F., Santamaría, A., Pedraza-Chaverri, J. et al. Increased Formation of Reactive Oxygen Species, but No Changes in Glutathione Peroxidase Activity, in Striata of Mice Transgenic for the Huntington's Disease Mutation. Neurochem Res 29, 729–733 (2004). https://doi.org/10.1023/B:NERE.0000018843.83770.4b

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  • DOI: https://doi.org/10.1023/B:NERE.0000018843.83770.4b

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