Kish S J, Zhong X H, Hornykiewicz O, Haycock J W
Human Neurochemical Pathology Laboratory, Clarke Institute of Psychiatry, Toronto, Ontario, Canada.
Ann Neurol. 1995 Aug;38(2):260-4. doi: 10.1002/ana.410380220.
Recent positron emission tomography (PET) studies using 3,4-[18F]fluorodihydroxyphenylalanine ([18F]fluorodopa) have reported little or no decrement in dopaminergic function in human striatum (caudate and putamen) during aging. In contrast, previous postmortem studies have reported marked age-dependent decreases in the activity of dopa decarboxylase (DDC), a variable upon which the PET determinations depend. Using quantitative blot immunolabeling techniques, we measured DDC protein concentrations in postmortem striata of 28 neurologically normal subjects ranging in age from 17 to 103 years. We found a significant, albeit modest, age-dependent decrease in the concentration of DDC protein in caudate (r = -0.50, p < 0.05) but not in putamen (r = -0.16, p > 0.05), with mean values of the 87-year-old group being 27% (caudate) and 12% (putamen) lower than those of the 30-year-old group. The absence of a robust effect of aging upon striatal DDC protein is consistent with the [18F]fluorodopa-PET studies that report either no change or only a relatively small decrease in striatal 18F accumulation during aging. To the extent that aging is associated with a substantial loss of striatal dopaminergic nerve terminals, the present results also suggest that DDC protein synthesis may be upregulated in those dopaminergic neurons that survive the aging process and, therefore, that striatal [18F]fluorodopa uptake indices may provide an overestimate of the number of dopaminergic nerve terminals during physiological aging.
最近使用3,4-[18F]氟二羟基苯丙氨酸（[18F]氟多巴）的正电子发射断层扫描（PET）研究报告称，在衰老过程中，人类纹状体（尾状核和壳核）的多巴胺能功能几乎没有下降或根本没有下降。相比之下，先前的尸检研究报告称，多巴脱羧酶（DDC）的活性存在明显的年龄依赖性下降，而PET测定依赖于该变量。我们使用定量印迹免疫标记技术，测量了28名年龄在17至103岁之间的神经功能正常受试者死后纹状体中的DDC蛋白浓度。我们发现，尾状核中DDC蛋白浓度存在显著的年龄依赖性下降，尽管幅度较小（r = -0.50，p < 0.05），但壳核中没有（r = -0.16，p > 0.05），87岁组的平均值比30岁组分别低27%（尾状核）和12%（壳核）。衰老对纹状体DDC蛋白没有强烈影响，这与[18F]氟多巴-PET研究结果一致，该研究报告称在衰老过程中纹状体中18F积累没有变化或仅相对小幅下降。就衰老与纹状体多巴胺能神经末梢大量丧失有关而言，目前的结果还表明，在衰老过程中存活下来的多巴胺能神经元中，DDC蛋白合成可能会上调，因此，在生理衰老过程中，纹状体[18F]氟多巴摄取指数可能高估了多巴胺能神经末梢的数量。
