Irwin I, Finnegan K T, Delanney L E, Di Monte D, Langston J W
California Institute for Medical Research, San Jose.
Brain Res. 1992 Feb 14;572(1-2):224-31. doi: 10.1016/0006-8993(92)90473-m.
Although the effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice have been reported to increase with age, they have not been characterized in the full spectrum of ages. Thus, in spite of a considerable body of scientific literature on the subject, previous reports leave unanswered the question of whether or not the increased susceptibility of fully mature mice is part of the aging process or simply a consequence of maturation. In the present study, the age-related effects of MPTP on striatal dopamine were studied in groups of C57BL/6 mice from young maturity to old age. The major increase in the effects of MPTP occurred between 2 and 10 months of age (equivalent to adolescence and young adulthood in humans). A slight additional increase was observed between 10 and 16 months (young adulthood and middle age) and the dopamine-depleting effects of MPTP significantly declined in truly aged animals (24 months). Of note also is the fact that normal concentrations of striatal dopamine did not decline in the later ages. Additional studies indicated that while neuronal sensitivity to the effects of 1-methyl-4-phenylpyridinium (MPP+; the putative toxic metabolite of MPTP) appears to remain constant, age-related changes in the activity of striatal monoamine oxidase type B (MAO B) paralleled the dopamine-depleting effects of MPTP in the 4 age groups. Indeed, MAO B activity increased between 2 and 16 months and declined slightly, but significantly, between 16 and 24 months. This pattern of age-related changes in MAO B, striatal dopamine and the sensitivity of the nigrostriatal system to toxic insult may provide insights into factors which have been implicated in age-related neurodegeneration and idiopathic Parkinson's disease.
尽管据报道1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）对小鼠的影响会随着年龄增长而增加，但尚未在整个年龄范围内进行特征描述。因此，尽管关于该主题有大量科学文献，但先前的报告并未回答完全成熟的小鼠易感性增加是衰老过程的一部分还是仅仅是成熟的结果这一问题。在本研究中，对从年轻成熟到老年的C57BL/6小鼠组进行了MPTP对纹状体多巴胺的年龄相关影响研究。MPTP作用的主要增加发生在2至10个月龄之间（相当于人类的青春期和年轻成年期）。在10至16个月之间（年轻成年期和中年期）观察到略有额外增加，而在真正老龄动物（24个月）中MPTP的多巴胺耗竭作用显著下降。同样值得注意的是，纹状体多巴胺的正常浓度在后期并未下降。额外的研究表明，虽然神经元对1-甲基-4-苯基吡啶离子（MPP +；MPTP的假定有毒代谢物）作用的敏感性似乎保持不变，但纹状体B型单胺氧化酶（MAO B）活性的年龄相关变化与MPTP在4个年龄组中的多巴胺耗竭作用平行。实际上，MAO B活性在2至16个月之间增加，在16至24个月之间略有但显著下降。MAO B、纹状体多巴胺以及黑质纹状体系统对毒性损伤敏感性的这种年龄相关变化模式可能为与年龄相关的神经退行性变和特发性帕金森病相关的因素提供见解。
