Gnanalingham K K, Milkowski N A, Smith L A, Hunter A J, Jenner P, Marsden C D
Parkinson's Disease Society Experimental Research Laboratories, King's College, London, United Kingdom.
J Neural Transm Gen Sect. 1995;101(1-3):65-82. doi: 10.1007/BF01271546.
The "short-term" (0.7 +/- 0.1 months post-MPTP) and "long-term" effects (36.7 +/- 4.4 months) of MPTP treatment on motor behaviour and [14C]-2DG uptake were investigated in the common marmoset. The subcutaneous administration of MPTP greatly reduced locomotor activity (-94% with respect to controls) and induced motor disability in the "short-term" MPTP-treated marmoset group. In the "long-term" MPTP group, MPTP treatment did not significantly affect locomotor activity (-27% with respect to controls) and there was partial recovery of motor disability. In the "short-term" MPTP group, there were increases in [14C]-2DG uptake in the GPl (+31 to +37%), SNc (+34 to +42%), VTA (+35%), LC (+23%), PPN (+19%) and in the VA (+19%), VL (+20%) and AM (+17%) thalamic nuclei. [14C]-2DG uptake was decreased in the STN (-15%). In the "long-term" MPTP group, [14C]-2DG uptake was increased in the GPl (+18%), SNc (+27%), VTA (+25%), PPN (+19%), ventral caudate nucleus (+18 to +23%), NAc (+22%), F.Ctx (+18%) and in the VA (+34%), VL (+28%), AV (+33%) and AM (+24%) thalamic nuclei. [14C]-2DG uptake was unchanged in the STN. The increase in metabolic activity of the surviving DA neurones and/or the reactive gliosis may account for the initial increase in [14C]-2DG uptake in the SNc and VTA. On the other hand, in the "long-term" MPTP-treated animals the increase in [14C]-2DG uptake in the SNc (though less than in the "short-term" MPTP group), ventral caudate and NAc may reflect the regenerative changes in the dopaminergic system in these areas. Despite the behavioural recovery, [14C]-2DG uptake remained elevated in the target areas for medial pallidal output (the thalamic nuclei and PPN). However, the attenuation of the changes in [14C]-2DG uptake in the GPl and STN of "long-term" MPTP-treated marmosets suggest that the striato-GPl and GPl-STN outputs closely reflect motor function in this primate model of Parkinson's disease.
在普通狨猴中研究了MPTP治疗对运动行为和[14C]-2DG摄取的“短期”（MPTP注射后0.7±0.1个月）和“长期”（36.7±4.4个月）影响。皮下注射MPTP可显著降低运动活性（相对于对照组降低94%），并在“短期”接受MPTP治疗的狨猴组中诱发运动功能障碍。在“长期”MPTP组中，MPTP治疗对运动活性没有显著影响（相对于对照组降低27%），并且运动功能障碍有部分恢复。在“短期”MPTP组中，苍白球内侧部（GPl）（增加31%至37%）、黑质致密部（SNc）（增加34%至42%）、腹侧被盖区（VTA）（增加35%）、蓝斑（LC）（增加23%）、脚桥核（PPN）（增加19%）以及丘脑腹前核（VA）（增加19%）、腹外侧核（VL）（增加20%）和前内侧核（AM）（增加17%）的[14C]-2DG摄取增加。底丘脑核（STN）的[14C]-2DG摄取减少（减少15%）。在“长期”MPTP组中，GPl（增加18%）、SNc（增加27%）、VTA（增加25%）、PPN（增加19%）以及腹侧尾状核（增加18%至23%）、伏隔核（NAc）（增加22%）、额叶皮质（F.Ctx）（增加18%）和丘脑VA（增加34%）、VL（增加28%）、前腹核（AV）（增加33%）和AM（增加24%）核的[14C]-2DG摄取增加。STN的[14C]-2DG摄取没有变化。存活的多巴胺能神经元代谢活性增加和/或反应性胶质细胞增生可能是SNc和VTA中[14C]-2DG摄取最初增加的原因。另一方面，在“长期”接受MPTP治疗的动物中，SNc（尽管低于“短期”MPTP组）、腹侧尾状核和NAc中[14C]-2DG摄取的增加可能反映了这些区域多巴胺能系统的再生变化。尽管行为有所恢复，但苍白球内侧部输出的靶区（丘脑核和PPN）中[14C]-2DG摄取仍然升高。然而，“长期”接受MPTP治疗的狨猴GPl和STN中[14C]-2DG摄取变化的减弱表明，纹状体-GPl和GPl-STN输出在这种帕金森病灵长类模型中密切反映运动功能。
