Burns L H, Pakzaban P, Deacon T W, Brownell A L, Tatter S B, Jenkins B G, Isacson O
Neuroregeneration Laboratory, McLean Hospital, Belmont, MA 02178, USA.
Neuroscience. 1995 Feb;64(4):1007-17. doi: 10.1016/0306-4522(94)00431-4.
While dyskinetic movements have been reported in primates with unilateral excitotoxic lesions following stimulation by dopaminergic agonists, the presence and intensity of the dyskinetic syndromes have varied extensively with size and location of lesion. With the intent of producing a more reliable behavioral model of Huntington disease, anatomically-defined lesions of limited size were produced by magnetic resonance imaging-guided stereotaxic injection of quinolinic acid in specific regions within the caudate and putamen of rhesus monkeys. The location and extent of the lesions were verified by magnetic resonance imaging as well as quantitative positron emission tomography imaging with the dopamine D1 specific receptor ligand SCH 39166 as a marker for striatal output neurons. The quality, frequency and duration of dyskinetic movements were assessed and quantified before and after administration of 0.5 mg/kg apomorphine in multiple test sessions over several months. Selective unilateral lesions in the posterior putamen, but not in the anterior putamen or the head of the caudate, produced marked dystonia and dyskinesia after apomorphine administration. While combined unilateral lesions of the caudate and posterior putamen produced dyskinesia similar to selective posterior putaminal lesions, combined unilateral lesions of the anterior and posterior putamen did not elicit dyskenesia. On the basis of these results, one monkey received a bilateral selective lesion in the posterior putamen. This animal remained healthy and exhibited marked spontaneous Huntington-like chorea spontaneously in the first 48 h after lesioning and persistent apomorphine-induced dyskinesia thereafter. We conclude that bilateral selective excitotoxic lesions of the posterior putamen provide an improved model of the movement disorder of Huntington disease.
虽然在多巴胺能激动剂刺激后，单侧兴奋性毒性损伤的灵长类动物中已报告有运动障碍性运动，但运动障碍综合征的存在和强度随损伤的大小和位置有很大差异。为了建立一个更可靠的亨廷顿病行为模型，通过磁共振成像引导的立体定向注射喹啉酸，在恒河猴尾状核和壳核的特定区域制造了大小有限的解剖学定义损伤。通过磁共振成像以及以多巴胺D1特异性受体配体SCH 39166作为纹状体输出神经元标记物的定量正电子发射断层扫描成像来验证损伤的位置和范围。在数月的多次测试过程中，在给予0.5mg/kg阿扑吗啡前后评估并量化运动障碍性运动的质量、频率和持续时间。选择性单侧损伤后壳核，但不是前壳核或尾状核头部，在给予阿扑吗啡后产生明显的肌张力障碍和运动障碍。虽然尾状核和后壳核的联合单侧损伤产生的运动障碍类似于选择性后壳核损伤，但前壳核和后壳核的联合单侧损伤并未引发运动障碍。基于这些结果，一只猴子接受了双侧后壳核选择性损伤。这只动物保持健康，在损伤后的头48小时内自发出现明显的亨廷顿样舞蹈症，此后持续出现阿扑吗啡诱导的运动障碍。我们得出结论，双侧后壳核选择性兴奋性毒性损伤为亨廷顿病的运动障碍提供了一个改进的模型。
