Dopamine-derived endogenous 1(R),2(N)-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, N-methyl-(R)-salsolinol, induced parkinsonism in rat: biochemical, pathological and behavioral studies
Dopamine-derived endogenous 1(R),2(N)-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, N-methyl-(R)-salsolinol, induced parkinsonism in rat: biochemical, pathological and behavioral studies
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DOI：
10.1016/0006-8993(95)01325-3
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发表时间：
1996-02
期刊：
影响因子：
2.9
通讯作者：
M. Naoi;W. Maruyama;P. Dostert;Y. Hashizume;D. Nakahara;Tsutomu Takahashi;M. Ota
中科院分区：
文献类型：
--
作者：
M. Naoi;W. Maruyama;P. Dostert;Y. Hashizume;D. Nakahara;Tsutomu Takahashi;M. Ota
多巴胺衍生的1-甲基-6，7-二羟基-1，2，3，4-四氢异喹啉（salsolinol，Sal）及其相关化合物通过注射到大鼠纹状体中检测其对多巴胺神经元的选择性神经毒性。在所检测的猪毛菜醇类似物中，只有N-甲基-（R）-猪毛菜醇（NM（R）Sal）诱导的行为变化与帕金森病非常相似：运动减退、僵硬的尾巴、休息时肢体抽搐和姿势异常。生化分析表明，注射NM（R）Sal后，NM（R）Sal本身及其氧化产物1，2-二甲基-6，7-二羟基异喹啉离子（DMDHIQ+）在纹状体内蓄积，黑质内也检测到一定量的DMDHIQ+。多巴胺和去甲肾上腺素减少，在纹状体和黑质更显着，而血清素及其代谢产物没有受到影响。形态学分析显示，连续给药NM（R）Sal后，纹状体黑质中含酪氨酸羟化酶（TH）的神经元选择性减少。这些结果表明NM（R）Sal对黑质多巴胺神经元的选择性细胞毒性，并讨论了这种6，7-二羟基异喹啉在帕金森病发病机制中的可能参与。
Dopamine-derived 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol, Sal) and related compounds were examined for their selective neurotoxicity to dopamine neurons by injection into the rat striatum. Among salsolinol analogs examined, only N-methyl-(R)-salsolinol (NM(R)Sal) induced behavioral changes very similar to those in Parkinson's disease: hypokinesia, stiff tail, limb twitching at rest and postural abnormality. Biochemical analysis showed that after NM(R)Sal injection, NM(R)Sal itself and its oxidation product, 1,2-dimethyl-6,7-dihydroxyisoquinolinium ion (DMDHIQ+) accumulated in the striatum, and also in the substantia nigra definite amount of DMDHIQ+was detected. Dopamine and noradrenaline were reduced in the striatum and more markedly in the substantia nigra, whereas serotonin and its metabolite were not affected. Morphological analysis revealed selective reduction of tyrosine hydroxylase (TH)-containing neurons in the substantia nigra after continuous NM(R)Sal administration in the striatum. These results demonstrate the selective cytotoxicity of NM(R)Sal to the dopamine neurons in the substantia nigra, and the possible involvement of this 6,7-dihydroxyisoquinoline in the pathogenesis of Parkinson's disease is discussed.