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Oxidative DNA damage in the aging mouse brain
Author(s) -
CardozoPelaez Fernando,
Song Shijie,
Parthasarathy Anand,
Hazzi Christopher,
Naidu Kamatham,
SanchezRamos Juan
Publication year - 1999
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/1531-8257(199911)14:6<972::aid-mds1010>3.0.co;2-0
Subject(s) - glutathione peroxidase , superoxide dismutase , medicine , putamen , endocrinology , neurochemical , oxidative stress , cerebellum , pons , dna damage , chemistry , dopamine , dopaminergic , neuroscience , biology , biochemistry , dna
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 nigrostriatal system. We hypothesized that oxidative damage to DNA was more likely to occur in the nigrostriatal system which undergoes significant neurochemical and functional changes 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), cerebellum (CB), and cerebral cortex (CX) at 3, 18, and 34 months of age in C57/bl mice. Steady‐state levels of oxo 8 dG increased significantly with age in MB, CP, and CB, but not in PM, HP, or CX. Manganese superoxide dismutase (MnSOD) activity decreased with age in MB, CP, and HP, but not in PM, CB, or CX. Regional activities of Cu/Zn superoxide dismutase (Cu/Zn SOD) and glutathione peroxidase (Glut Px) did not change significantly with age. Concomitant 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. In conclusion, oxyradical‐associated damage to DNA did not accumulate uniformly across brain regions with age and was highest in brain regions that subserve spontaneous locomotor activity and motor coordination.