Degryse A D, Colpaert F C
Brain Res Bull. 1986 May;16(5):561-71. doi: 10.1016/0361-9230(86)90131-0.
The study concerns symptoms and behavioral characteristics induced by MPTP in a 20-year-old Macaca cynomolgus fascicularis, their evolution over 7 months, and the animal's response to 1-dopa treatment. The symptoms which the animal developed include those that have been described earlier in Macaca mulatta and Saimiri sciureus, i.e., rigidity, action tremor, postural tremor, postural flexion, hypokinesia, and bradykinesia. In addition, however, the animal developed a 3.8 Hz resting tremor which in humans is pathognomonic of Parkinson's disease, as well as cogwheeling, the glabellar tap sign, drooling, impaired ability to relax, and many other symptoms. Also unlike previously described MPTP monkeys, the animal's symptoms neither improved spontaneously, nor did they remain stable shortly after MPTP injection. Instead, symptoms steadily progressed to reach a severe status 2 months after MPTP, and further progression was apparent after another 5 months. Therapeutic responses to 1-dopa required accumulation of or kindling by the 100 mg unit doses that were spaced 4 hr apart, were often organized in time as ON episodes that alternated with OFF episodes, and were associated with dyskinesias and bizarre behavior. Of particular interest is that the animal showed kinesia paradoxa which, in humans, constitutes a feature that is unique to Parkinson's disease among the extrapyramidal disorders. In addition to available evidence, the present findings validate the syndrome induced by MPTP in monkey as an animal analogue of Parkinson's disease. Taxonomic category, age, and the occurrence of shock in response to MPTP are discussed as variables that may possibly co-determine the pathology which MPTP may induce in monkey.
该研究关注了20岁食蟹猴因MPTP诱导产生的症状和行为特征、这些症状在7个月内的演变过程以及该动物对左旋多巴治疗的反应。该动物出现的症状包括先前在恒河猴和松鼠猴中描述过的症状,即僵硬、动作性震颤、姿势性震颤、姿势性屈曲、运动减少和运动迟缓。然而,除此之外,该动物还出现了3.8赫兹的静止性震颤(在人类中是帕金森病的特征性表现)以及齿轮样强直、眉间叩击征、流涎、放松能力受损等许多其他症状。与先前描述的MPTP猴也不同的是,该动物的症状既没有自发改善,也没有在注射MPTP后不久保持稳定。相反,症状在MPTP注射后2个月稳步发展至严重状态,再过5个月后进一步发展明显。对左旋多巴的治疗反应需要间隔4小时给予100毫克单位剂量进行累积或激发,通常会按时出现与“关”期交替的“开”期,并伴有运动障碍和怪异行为。特别有趣的是,该动物表现出矛盾运动,在人类中,这是帕金森病在锥体外系疾病中独有的特征。除已有证据外,本研究结果证实了MPTP在猴中诱导的综合征可作为帕金森病的动物模型。文中讨论了分类类别、年龄以及对MPTP反应中休克的发生等可能共同决定MPTP在猴中诱导的病理变化的变量。