Time-Course Analysis of Protein and Lipid Oxidation in the Brains of Yac128 Huntington's Disease Transgenic Mice.

Abstract

Huntington's disease (HD) is caused by an expansion of cytosine-adenine-guanine (CAG) repeats within the coding region of the HD gene, which expresses the protein huntingtin and is characterized by selective degeneration of specific neuronal populations, mainly in the striatum and the cortex. The mechanisms that account for this selective neuronal death are multifaceted, but oxidative stress might play an important role in this process. To determine whether changes in the intracellular redox state will result in oxidative damage to cellular macromolecules with disease progression, we analyzed levels of lipid peroxidation (with the thiobarbituric acid reactive substances [TBARS] assay) and protein carbonyl formation (using the 2,4-dinitrophenylhydrazine reaction) in the cerebellum, cerebral cortex, prefrontal cortex, striatum, and hippocampus of the YAC128 HD mouse model at 3, 6, and 12 months of age. With the exception of a transient increase in protein carbonyl levels in the YAC128 prefrontal cortex at 6 months of age, levels of lipid peroxidation and protein oxidation were not significantly different between YAC128 mice and their age-matched wild-type counterparts in any of the brain regions analyzed up to 12 months of age. However, age-related increases in oxidative stress were observed in various brain regions. These results suggest that lipid and protein oxidative damage is not a major contributor to neurodegeneration in the YAC128 brain up to 12 months of age.