Dopamine turnover is upregulated in the caudate/putamen of asymptomatic MPTP-treated rhesus monkeys
Dopamine turnover is upregulated in the caudate/putamen of asymptomatic MPTP-treated rhesus monkeys
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DOI：
10.1016/j.neuint.2006.03.013
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发表时间：
2006-10-01
影响因子：
4.2
通讯作者：
Hornykiewicz, Oleh
中科院分区：
文献类型：
--
作者：
Pifl, Christian;Hornykiewicz, Oleh
在帕金森病（PD）和实验性帕金森综合征中，黑质中多巴胺能神经元和纹状体中多巴胺（DA）的损失分别高达60%和80%，但仍无症状。已经提出了几种机制，这种功能性补偿，DA介导的是最确定的一个。由于这一机制最近受到1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）治疗的猴子纹状体DA分析的挑战，我们提出了三组恒河猴的几个DA能参数的数据：MPTP治疗的无症状动物;症状MPTP治疗的动物与稳定的帕金森病;和未治疗的性别和年龄匹配的对照。除了常用的高香草酸（HVA）/DA比率之外，我们还确定了纹状体和黑质3，4-二羟苯基乙酸（DOPAC）与DA水平的比率以及酪氨酸羟化酶（TH）酶活性与DA水平的比率，因此，在部分去神经支配的条件下，该比率可能不太可靠。我们发现，在无症状的MPTP猴的壳核和尾状核的DOPAC/DA比值的偏移具有高度的统计学意义的1.9-5.8倍，与对照组相比，该比值的偏移在相同的范围内的2.6-5.4倍的偏移在有症状的动物。此外，TH/DA比值显着增加，在这两个，无症状和有症状的MPTP治疗的猴子，在壳核和尾状核的3-和2.7-7.0倍，分别移位。在黑质中，DOPAC水平和TH活性在MPTP后显著降低（-77%至-97%），但该脑区的DOPAC/DA和TH/DA比值没有变化。总的来说，我们的研究结果支持DA能补偿帕金森病过程中的症状前阶段进行性纹状体DA损失的概念。(c)2006爱思唯尔有限公司保留所有权利。
In Parkinson's disease (PD) and experimental parkinsonism, losses of up to 60% and 80%, respectively, of dopaminergic neurons in substantia nigra, and dopamine (DA) in striatum remain asymptomatic. Several mechanisms have been suggested for this functional compensation, the DA-mediated being the most established one. Since this mechanism was recently challenged by striatal DA analysis in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys, we present data on several DAergic parameters in three groups of rhesus monkeys: MPTP-treated asymptomatic animals; symptomatic MPTP-treated animals with stable parkinsonism; and untreated sex and age matched controls. We determined ratios of striatal and nigral 3,4-dihydroxyphenyl acetic acid (DOPAC) to DA levels and tyrosine hydroxylase (TH) enzyme activity to DA levels, in addition to the commonly used homovanillic acid (HVA)/DA ratios which, as such, might be less reliable under the conditions of partial denervation. We found that in the asymptomatic MPTP monkeys the DOPAC/DA ratios in putamen and caudate nucleus were shifted with high statistical significance 1.9-5.8-fold, as compared to controls, the shifting of the ratios being in the same range as the 2.6-5.4-fold shifts in the symptomatic animals. Also TH/DA ratios were significantly increased in both, the asymptomatic and the symptomatic MPTP-treated monkeys, with shifts in the putamen and caudate nucleus of 3- and 2.7-7.0-fold, respectively. In the substantia nigra, DOPAC levels and TH activity were strongly decreased after MPTP (-77 to -97%), but the ratios DOPAC/DA and TH/DA were not changed in this brain region. Collectively, our findings support the concept of DAergic compensation of the progressive striatal DA loss in the presymptomatic stages of the parkinsonian disease process. (c) 2006 Elsevier Ltd. All rights reserved.