Emborg-Knott M E, Domino E F
Department of Pharmacology, University of Michigan, Ann Arbor, Michigan, 48109-0632, USA.
Exp Neurol. 1998 Aug;152(2):214-20. doi: 10.1006/exnr.1998.6845.
Five female adult Macaca nemestrina monkeys, given a unilateral intracarotid (ic) infusion of 2.3-3.5 mg of MPTP-HCl, were studied for 6-8 years. Two to 3 days after MPTP, the animals developed hemiparkinsonism characterized by rigidity and flexed posture of the arm contralateral to the side of infusion with episodes of tremor, circling ipsilateral to the lesioned side, a slight balance disturbance, and stooped posture. Rating of parkinsonian features 4 months after ic infusion, and yearly thereafter, did not show any statistically significant changes. The animals maintained their usual appetite and body weight increased normally. Each animal responded to l-DOPA methyl ester with decreased parkinsonian signs and symptoms and increased contralateral turning. In contrast, after control vehicle administration, the animals continued to have the same parkinsonian signs and predominant ipsilateral turns. In three of the five monkeys, contralateral turns after vehicle significantly increased after 6-8 years. Unilateral intracarotid MPTP induced asymmetric motor behavior that remained stable after 6-8 years. Animals that showed an increased frequency of contralateral circling after control vehicle showed a decrease in contralateral turns after l-DOPA methyl ester, suggesting neuroplastic changes over the years.
对5只成年雌性豚尾猕猴进行了研究,它们接受了单侧颈内动脉注射2.3 - 3.5毫克盐酸MPTP,研究时长为6至8年。注射MPTP后2至3天,这些动物出现了偏侧帕金森综合征,其特征为注射侧对侧手臂出现僵硬和屈曲姿势,伴有震颤发作,向损伤侧同侧转圈,轻微的平衡障碍以及弯腰姿势。颈内动脉注射4个月后以及此后每年对帕金森特征进行评分,均未显示出任何统计学上的显著变化。这些动物保持了正常的食欲,体重也正常增加。每只动物对左旋多巴甲酯的反应是帕金森症状体征减轻,对侧旋转增加。相比之下,给予对照载体后,这些动物继续出现相同的帕金森症状体征且主要为同侧旋转。在5只猴子中的3只中,给予载体后对侧旋转在6至8年后显著增加。单侧颈内动脉注射MPTP诱发了不对称运动行为,这种行为在6至8年后保持稳定。在给予对照载体后对侧转圈频率增加的动物,在给予左旋多巴甲酯后对侧旋转减少,这表明多年来存在神经可塑性变化。