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MPTP诱导的帕金森症:有症状和无症状黑长尾猴的黑质、腹侧被盖区及红核后区亚区域中多巴胺浓度的相对变化

MPTP-induced parkinsonism: relative changes in dopamine concentration in subregions of substantia nigra, ventral tegmental area and retrorubral field of symptomatic and asymptomatic vervet monkeys.

作者信息

Elsworth J D, Deutch A Y, Redmond D E, Sladek J R, Roth R H

机构信息

Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510.

出版信息

Brain Res. 1990 Apr 16;513(2):320-4. doi: 10.1016/0006-8993(90)90474-p.

Abstract

Dopamine (DA) and homovanillic acid (HVA) concentrations were measured in subregions of substantia nigra, ventral tegmental area and retrorubral field in vervet monkeys 1 to 2 months after treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Identical MPTP treatment regimens produced animals with different degrees of parkinsonism. In asymptomatic monkeys, changes in DA and HVA concentrations in the midbrain DA regions were relatively small and involved central substantia nigra and dorsomedial ventral tegmental area. In contrast, changes in symptomatic monkeys were more severe and widespread, significantly affecting all examined subregions of substantia nigra (greater than 75% DA depletion), both dorsomedial and ventromedial ventral tegmental area and lateral, but not medial, retrorubral field. The data indicate that DA neurons in subregions of substantia nigra, ventral tegmental area and retrorubral field are not equally susceptible to MPTP toxicity. The pattern of MPTP-induced DA and HVA losses in the vervet monkey mesostriatal dopaminergic system may resemble postencephalitic Parkinson's disease more closely than idiopathic Parkinson's disease.

摘要

在黑猩猩用1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)治疗1至2个月后,测量其黑质、腹侧被盖区和红核后区各亚区域的多巴胺(DA)和高香草酸(HVA)浓度。相同的MPTP治疗方案产生了不同程度帕金森病的动物。在无症状的猴子中,中脑多巴胺区域的DA和HVA浓度变化相对较小,涉及中央黑质和背内侧腹侧被盖区。相比之下,有症状猴子的变化更严重且更广泛,显著影响黑质的所有检查亚区域(DA耗竭大于75%)、背内侧和腹内侧腹侧被盖区以及外侧而非内侧红核后区。数据表明,黑质、腹侧被盖区和红核后区各亚区域的DA神经元对MPTP毒性的易感性不同。黑猩猩中脑纹状体多巴胺能系统中MPTP诱导的DA和HVA损失模式可能比特发性帕金森病更类似于脑炎后帕金森病。

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