Hantraye P, Riche D, Maziere M, Isacson O
Lira-CNRS Unit 1285, Service Hospitalier Frédéric Joliot, Orsay, France.
Exp Neurol. 1990 May;108(2):91-104. doi: 10.1016/0014-4886(90)90014-j.
Unilateral caudate-putamen (CP) lesions induced by the glutamate receptor agonist ibotenic acid in baboons produced a neuropathological and behavioral model of Huntington's disease (HD) in the nonhuman primate. Neuropathological evaluation of the lesioned caudate-putamen revealed a neurodegenerative pattern resembling HD. The ibotenic acid-infused CP areas showed a neuronal loss in Nissl-stained sections and a marked astrocytic gliosis by immunohistochemical staining for glial-fibrillary-acidic protein. Acetylcholinesterase fiber staining was severely reduced in the lesioned CP, while afferent dopaminergic fibers, as shown by tyrosine hydroxylase staining, were relatively spared. There was a moderate reduction of met-enkephalin staining in the globus pallidus-pars lateralis ipsilateral to the ibotenic acid lesion, indicating a partial denervation of this structure following the lesion. In the behavioral studies a dyskinetic syndrome with features in common with HD was provoked in the lesioned animals following dopamine receptor agonist administration (1-2 mg/kg apomorphine). The symptoms included hyperkinesia, chorea, dystonia, postural asymmetries, head, and orofacial dyskinesia. The apomorphine test was highly reproducible and individual animals responded with a similar set and incidence of dyskinesia in successive tests. Since the behavioral observations following excitotoxic caudate-putamen damage parallel symptoms in HD patients given dopamine stimulatory drugs, a hypothesis is presented for the observed abnormal movements suggesting that the CP lesions reduce movement thresholds while the activation of dopaminoceptive regions induces dyskinesias.
在狒狒中，由谷氨酸受体激动剂鹅膏蕈氨酸诱导的单侧尾状核-壳核（CP）损伤产生了非人类灵长类动物亨廷顿病（HD）的神经病理学和行为模型。对受损尾状核-壳核的神经病理学评估显示出一种类似于HD的神经退行性模式。注入鹅膏蕈氨酸的CP区域在尼氏染色切片中显示神经元丢失，通过胶质纤维酸性蛋白免疫组织化学染色显示明显的星形胶质细胞增生。受损CP中的乙酰胆碱酯酶纤维染色严重减少，而酪氨酸羟化酶染色显示传入多巴胺能纤维相对保留。在与鹅膏蕈氨酸损伤同侧的苍白球外侧部，甲硫氨酸脑啡肽染色有中度减少，表明损伤后该结构部分去神经支配。在行为研究中，给受损动物注射多巴胺受体激动剂（1-2mg/kg阿扑吗啡）后引发了一种具有HD共同特征的运动障碍综合征。症状包括运动亢进、舞蹈症、肌张力障碍、姿势不对称、头部和口面部运动障碍。阿扑吗啡试验具有高度可重复性，并且在连续试验中，个体动物出现类似的运动障碍组合和发生率。由于兴奋性毒性尾状核-壳核损伤后的行为观察与给予多巴胺刺激药物的HD患者的症状相似，因此提出了一个关于观察到的异常运动的假设，表明CP损伤降低了运动阈值，而多巴胺感受区域的激活诱导了运动障碍。
