期刊
NEUROBIOLOGY OF AGING
卷 24, 期 5, 页码 697-706出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/S0197-4580(02)00186-0
关键词
dopamine toxicity; neurodegeneration; psychomotor performance; motor behavior; oxidative stress; aging
The oxidative stress (OS) theory has implicated the involvement of reactive oxygen species (ROS) in both aging and age-dependent neurodegenerative diseases. The dopaminergic system is particularly vulnerable to ROS, and dopamine (DA) itself can be an endogenous source of ROS. The present study evaluated the hypothesis that DA-induced toxicity is age-dependent, and tested the behavioral and histological correlates of DA neurotoxicity in aging. Young (6 months) and middle-aged (15 months) rats were chronically treated with DA in the substantia nigra (SN, 1 mumol/2 mul vehicle per side/day/5 days) and were subsequently examined for changes in motor function and histology. The neurotoxic effect of DA treatment was an age-dependent effect, as middle-aged animals that received DA infusions in the SN were more impaired than their age-matched controls, especially on tasks that involved greater sensory-motor coordination, whereas young animals that received DA behaved similarly to their age-matched controls. The behavioral effects noted were accompanied by a loss of the tyrosine hydroxylase phenotype in substantia nigra. However, selective neurodegeneration was not noted in the SN of the treated animals, nor was a selective iron deposition noted at the site of injection. These results suggest that a neurochemical deficit and not cell loss per se within the nigrostriatal system underlies the motor behavioral deficits observed in the middle-aged rats. (C) 2002 Elsevier Science Inc. All rights reserved.
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