SYMPTOMATIC AND ASYMPTOMATIC 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE-TREATED PRIMATES - BIOCHEMICAL-CHANGES IN STRIATAL REGIONS
SYMPTOMATIC AND ASYMPTOMATIC 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE-TREATED PRIMATES - BIOCHEMICAL-CHANGES IN STRIATAL REGIONS
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DOI：
10.1016/0306-4522(89)90212-1
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发表时间：
1989-01-01
期刊：
影响因子：
3.3
通讯作者：
ROTH, RH
中科院分区：
文献类型：
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作者：
ELSWORTH, JD;DEUTCH, AY;ROTH, RH
给灵长类动物注射神经毒素1-甲基-4-苯基-1，2，3，6-四氢吡啶，可建立一个极好的特发性帕金森病行为模型。在黑长尾猴中，在给药后1 - 2个月检查了两个1-甲基-4-苯基-1，2，3，6-四氢吡啶给药组纹状体的区域生化差异，并与对照组进行比较;一组在1-甲基-4-苯基-1，2，3，6-四氢吡啶给药后未观察到粗大运动异常（无症状），而另一组出现明显帕金森病（有症状）。在两个1-甲基-4-苯基-1，2，3，6-四氢吡啶处理组中，在纹状体中观察到多巴胺和高香草酸浓度的大量消耗;通常，有症状组的多巴胺损失（> 95%）大于无症状组（> 75%）。然而，在纹状体，1-甲基-4-苯基-1，2，3，6-四氢吡啶的敏感性显着的异质性被发现，某些纹状体区域有99%的多巴胺耗尽，即使在无症状的猴子。总体而言，在纹状体腹内侧区的多巴胺和高香草酸浓度的损失小于背外侧区在同一冠状面。有一个显着的负相关控制高香草酸/多巴胺的比例和敏感性的检查区域1-甲基-4-苯基-1，2，3，6-四氢吡啶毒性。与特发性不同，但与脑炎后帕金森病相似，尾状核中的多巴胺和高香草酸水平相对于壳核并没有幸免;事实上，在无症状组中，尾状核多巴胺和高香草酸浓度的消耗程度大于壳核。相对较小，但明显的差异，在无症状和有症状的猴子在某些地区之间的多巴胺和高香草酸消耗表明潜在的逆转帕金森病运动异常与纹状体内移植或植入，产生相对较低的多巴胺。
Administration of the neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, to primates produces an excellent behavioral model of idiopathic Parkinson''s disease. In the vervet monkey, regional biochemical differences in the striatum of two 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated groups were examined one to two months after treatment and compared with controls; one group displayed no observable gross motor abnormalities after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment (asymptomatic), whereas the other group became markedly parkinsonian (symptomatic). In both 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated groups massive depletions of dopamine and homovanillic acid concentrations were observed in the striatum; generally, dopamine losses in the symptomatic group (> 95%) were greater than in the asymptomatic group (> 75%). However, in striatum, a marked heterogeneity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine susceptibility was found; certain striatal regions having 99% depletion of dopamine even in asymptomatic monkeys. Overall, in ventromedial regions of striatum the losses of dopamine and homovanillic acid concentrations were less than in dorsolateral regions at the same coronal level. There was a significant negative correlation between control homovanillic acid/dopamine ratios and susceptibility of examined regions to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity. Unlike idiopathic, but similar to postencephalitic, Parkinson''s disease, dopamine and homovanillic acid levels in caudate nucleus were not spared relative to putamen; in fact, in the asymptomatic group caudate nucleus dopamine and homovanillic acid concentrations were depleted to a greater extent than in putamen. The relatively small, but distinct, differences in dopamine and homovanillic acid depletions between asymptomatic and symptomatic monkeys in some regions indicates the potential of reversing parkinsonian motor abnormalities with intrastriatal grafts or implants that produce relatively low amounts of dopamine.