Parkinsonism in monkeys produced by chronic administration of an endogenous substance of the brain, tetrahydroisoquinoline: The behavioral and biochemical changes
Parkinsonism in monkeys produced by chronic administration of an endogenous substance of the brain, tetrahydroisoquinoline: The behavioral and biochemical changes
复制标题
长期给予大脑内源性物质四氢异喹啉引起的猴子帕金森症：行为和生化变化
DOI：
10.1016/0304-3940(90)90768-5
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发表时间：
1990
影响因子：
2.5
通讯作者：
T. Nagatsu
中科院分区：
文献类型：
--
作者：
Mitsuo Yoshida;T. Niwa;T. Nagatsu
我们研究了一种可能的内源性多巴胺能神经毒素，四氢异喹啉（TIQ，每天20mg /kg， s.c.，持续104天）对松鼠猴的影响。长期服用TIQ的松鼠猴即使在停用TIQ 7天后也会出现类似帕金森病的运动症状，左旋多巴治疗显著减轻了这些症状。对TIQ处理的猴子进行脑生化分析发现，多巴胺（DA）和总生物蝶呤（BP）浓度以及黑质酪氨酸羟化酶（TH）活性显著降低，并且这些生化变化在慢性TIQ给药终止后7天内没有逆转。采用气相色谱-质谱联用技术对注射盐水的对照猴脑（尾核-壳核）中的TIQ进行了鉴定。TIQ在尾壳核的内源性水平约为0.15 μg/g，在TIQ给药结束后1天和7天，TIQ的内源性水平均升高至3-4 μg/g。
We have examined the effect of chronic administration of a probable endogenous dopaminergic neurotoxin, tetrahydroisoquinoline (TIQ, 20 mg/kg per day, s.c. for up to 104 days), on squirrel monkeys. Chronically administered TIQ produced motor symptoms similar to parkinsonism in squirrel monkeys even after 7 days' discontinuation of TIQ and the symptomes were alleviated remarkably by levodopa treatment. Biochemical analysis of the brains of TIQ-treated monkeys revealed significant decrease in dopamine (DA) and total biopterin (BP) concentrations, and tyrosine hydroxylase (TH) activity in the substantia nigra, and these biochemical changes were not reversed by 7 days following the termination of chronic administration of TIQ. TIQ was identified in the brain (caudate-putamen) of saline-injected control monkeys by gas chromatography-mass spectrometry. The endogenous levels of TIQ in the caudate-putamen was about 0.15 μg/g, and increased up to 3–4 μg/g, 1 day as well as 7 days following termination of TIQ administration.