Prell G D, Khandelwal J K, Burns R S, Blandina P, Morrishow A M, Green J P
Department of Pharmacology, Mount Sinai School of Medicine, City University of New York, NY.
J Neural Transm Park Dis Dement Sect. 1991;3(2):109-25. doi: 10.1007/BF02260886.
The cerebrospinal fluid (CSF) levels of pros-methylimidazoleacetic acid (p-MIAA) in thirteen medication-free patients with mild to moderate Parkinson's disease were highly correlated (Spearman's rho = 0.749, p less than 0.005) with the severity of signs of the disease as scored on the Columbia University Rating Scale. Levels of p-MIAA in males (n = 8) and females (n = 5) were each significantly correlated with scores of severity (rho = 0.78, p less than 0.05 and rho = 1.0, p less than 0.05, respectively). In C57BL/6 mice treated with 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine (MPTP), levels of p-MIAA were significantly correlated with the depleted levels of dopamine (r = 0.85, p less than 0.01), homovanillic acid (r = 0.79, p less than 0.02), 3,4-dihydroxyphenylacetic acid (r = 0.84, p less than 0.01) and norepinephrine (r = 0.91, p less than 0.002) in striatum, but not in cortex of the same mice. No such correlations were observed in either striatum or cortex of saline-treated control mice. Mean levels of p-MIAA in CSF did not differ significantly between patients and age-matched controls; and mean levels of p-MIAA in striatum did not differ between MPTP-treated mice and controls. The simplest hypothesis to account for these strong correlations in the absence of differences in mean levels of p-MIAA is that accumulation of p-MIAA [or process(es) that govern its accumulation] influences a failing nigrostriatal system. It is also possible (in analogy with findings in other diseases and with other drugs) that measurements of the putative metabolite(s) of p-MIAA may distinguish the patients and the MPTP-treated mice from their respective controls. Elucidation of the processes that regulate formation and disposition of p-MIAA in brain and information on the neural effects of p-MIAA, its precursors and its putative metabolites may yield insight into factors that regulate the progression of Parkinson's disease, and may shed additional light on the cause(s) of this disease.
13名未服用药物的轻至中度帕金森病患者脑脊液中前甲基咪唑乙酸（p-MIAA）水平与哥伦比亚大学评定量表所记录的疾病体征严重程度高度相关（斯皮尔曼等级相关系数rho = 0.749，p < 0.005）。男性（n = 8）和女性（n = 5）的p-MIAA水平均与严重程度评分显著相关（rho分别为0.78，p < 0.05和rho = 1.0，p < 0.05）。在用1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）处理的C57BL/6小鼠中，p-MIAA水平与纹状体中多巴胺（r = 0.85，p < 0.01）、高香草酸（r = 0.79，p < 0.02）、3,4-二羟基苯乙酸（r = 0.84，p < 0.01）和去甲肾上腺素（r = 0.91，p < 0.002）的消耗水平显著相关，但在同一只小鼠的皮质中无此相关性。在生理盐水处理的对照小鼠的纹状体或皮质中均未观察到此类相关性。患者与年龄匹配的对照者脑脊液中p-MIAA的平均水平无显著差异；MPTP处理的小鼠与对照小鼠纹状体中p-MIAA的平均水平也无差异。在p-MIAA平均水平无差异的情况下，解释这些强相关性的最简单假设是p-MIAA的积累[或控制其积累的过程]影响了功能衰退的黑质纹状体系统。也有可能（类似于其他疾病和其他药物的研究结果），对p-MIAA假定代谢产物的测量可以将患者和MPTP处理的小鼠与其各自的对照区分开来。阐明调节p-MIAA在脑中形成和处置的过程，以及关于p-MIAA、其前体及其假定代谢产物的神经效应的信息，可能有助于深入了解调节帕金森病进展的因素，并可能进一步揭示该疾病的病因。
