Cardozo-Pelaez F, Song S, Parthasarathy A, Hazzi C, Naidu K, Sanchez-Ramos J
Department of Neurology, University of South Florida, and James Haley Veterans Affairs Hospital, Tampa 33620, USA.
Mov Disord. 1999 Nov;14(6):972-80. doi: 10.1002/1531-8257(199911)14:6<972::aid-mds1010>3.0.co;2-0.
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-hydroxy2'-deoxyguanosine (oxo8dG), 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/b1 mice. Steady-state levels of oxo8dG 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.
大脑对许多损伤表现出区域易损性，年龄本身对神经元群体也有不同影响，黑质纹状体系统中多巴胺能神经元随年龄增长而丧失就是例证。我们推测，随着年龄增长经历显著神经化学和功能变化的黑质纹状体系统更易发生DNA氧化损伤。为验证这一假设，我们检测了C57/b1小鼠在3个月、18个月和34个月时脑桥延髓（PM）、中脑（MB）、尾状核 - 壳核（CP）、海马（HP）、小脑（CB）和大脑皮层（CX）中8 - 羟基 - 2'-脱氧鸟苷（oxo8dG）水平所指示的DNA氧化损伤情况。oxo8dG的稳态水平在MB、CP和CB中随年龄显著增加，但在PM、HP或CX中没有变化。锰超氧化物歧化酶（MnSOD）活性在MB、CP和HP中随年龄下降，但在PM、CB或CX中没有变化。铜/锌超氧化物歧化酶（Cu/Zn SOD）和谷胱甘肽过氧化物酶（Glut Px）的区域活性随年龄没有显著变化。与DNA损伤的区域变化相伴的是，运动活动、运动协调性和纹状体多巴胺含量随年龄显著下降，尤其是在18个月至34个月期间。总之，与氧自由基相关的DNA损伤不会随年龄在脑区中均匀积累，在负责自发运动活动和运动协调的脑区中最高。
