Tabbal S D, Mink J W, Antenor J A V, Carl J L, Moerlein S M, Perlmutter J S
Department of Neurology, Washington University in St. Louis School of Medicine, St. Louis, MO 63110-1093, USA.
Neuroscience. 2006 Sep 1;141(3):1281-7. doi: 10.1016/j.neuroscience.2006.04.072. Epub 2006 Jun 12.
Unilateral intracarotid infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in baboons produces transient contralateral dystonia lasting 2-3 weeks followed by chronic hemiparkinsonism. We now extend this model to Macaca nemestrina and Macaca fascicularis. MPTP was infused unilaterally into the internal carotid artery of two M. nemestrina and 11 M. fascicularis. Effects were assessed with blinded clinical ratings of dystonia and Parkinsonism; [18F]-6-fluoro-DOPA (FDOPA) positron emission tomography; and postmortem measurements of striatal dopamine content. In two M. nemestrina, MPTP 0.4 mg/kg intracarotid produced acute dystonia within 24 h then chronic Parkinsonism starting 3 weeks later. In three M. fascicularis, MPTP 0.4 mg/kg produced acute dystonia within 3-8 h but two others died from large hemispheric infarcts within 1 day. A much lower dose, MPTP 0.1 mg/kg produced no clinical manifestations (n=1), whereas MPTP 0.25 mg/kg produced consistent transient dystonia and ipsiversive turning within 1-3 days followed by chronic Parkinsonism at 3 weeks (n=5). One week after MPTP, striatal FDOPA uptake decreased an average of 69% in M. nemestrina (0.4 mg/kg); and decreased an average of 70+/-21% in M. fascicularis (0.25 mg/kg). Striatal dopamine was reduced an average 66% in the first day (n=2) during acute dystonia, 98% at 3 days (n=1) and 99%+/-2.3% at 2-4 months (n=5). M. nemestrina had a clinical response similar to baboons whereas M. fascicularis seemed more sensitive to MPTP. These findings extend the model of MPTP-induced transient dystonia followed by chronic hemiparkinsonism to M. nemestrina and M. fascicularis and demonstrate that the early dystonic phase is accompanied by striatal dopamine deficiency.
在狒狒中单侧颈内动脉注入1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）会产生持续2至3周的短暂对侧肌张力障碍，随后出现慢性偏侧帕金森综合征。我们现在将这个模型扩展到豚尾猕猴和食蟹猕猴。将MPTP单侧注入两只豚尾猕猴和11只食蟹猕猴的颈内动脉。通过对肌张力障碍和帕金森综合征进行盲法临床评分、[18F]-6-氟多巴（FDOPA）正电子发射断层扫描以及纹状体多巴胺含量的尸检测量来评估效果。在两只豚尾猕猴中，颈内动脉注入0.4mg/kg的MPTP在24小时内产生急性肌张力障碍，然后在3周后开始出现慢性帕金森综合征。在三只食蟹猕猴中，0.4mg/kg的MPTP在3至8小时内产生急性肌张力障碍，但另外两只在1天内死于大面积半球梗死。低得多的剂量，0.1mg/kg的MPTP未产生临床表现（n = 1），而0.25mg/kg的MPTP在1至3天内产生持续的短暂肌张力障碍和向同侧转动，随后在3周时出现慢性帕金森综合征（n = 5）。MPTP注射一周后，豚尾猕猴（0.4mg/kg）纹状体FDOPA摄取平均下降69%；食蟹猕猴（0.25mg/kg）纹状体FDOPA摄取平均下降70±21%。在急性肌张力障碍的第一天，纹状体多巴胺平均减少66%（n = 2），在3天时减少98%（n = 1），在2至4个月时减少99%±2.3%（n = 5）。豚尾猕猴的临床反应与狒狒相似，而食蟹猕猴似乎对MPTP更敏感。这些发现将MPTP诱导的短暂肌张力障碍随后出现慢性偏侧帕金森综合征的模型扩展到豚尾猕猴和食蟹猕猴，并证明早期肌张力障碍阶段伴有纹状体多巴胺缺乏。
