Oxidative DNA damage in the aging mouse brain

The brain exhibits regional vulnerabilities to many insults, and age itself has differential effects on neuronal populations as exemplified by the age -dependent loss of dopaminergic neurons in the nigostriatal system. We hypo thesized that oxidative damage to DNA was more likely to occur in the nigro striatal system which undergoes significant neurochemical and functional ch anges with age. To test this hypothesis, oxidative damage to DNA, indicated by levels of 8-hydroxy-2'-deoxyguanosine (oxo(8)dG), was measured in pons- medulla (PM), midbrain (MB), caudate-putamen (CP), hippocampus (HP), cerebe llum (CB), and cerebral cortex (CX) at 3, 18, and 34 months of age in C57/b l mice. Steady-state levels of oxo8dG increased significantly with age in M B, CP, and CB, but not in PM, HP, or CX. Manganese superoxide dismutase (Mn SOD) activity decreased with age in MB, CP, and HP, but not in PM, CB, or C X. Regional activities of Cu/Zn superoxide dismutase (Cu/Zn SOD) and glutat hione peroxidase (Glut Px) did not change significantly with age. Concomita nt with the regional alterations in DNA damage, there was a significant age -dependent decline in locomotor activity, motor coordination, and striatal dopamine content especially during the interval between 18 and 34 months. I n conclusion, oxyradical-associated damage to DNA did not accumulate unifor mly across brain regions with age and was highest in brain regions that sub serve spontaneous locomotor activity and motor coordination.