Sundström E, Luthman J, Goldstein M, Jonsson G
Department of Histology and Neurobiology, Karolinska Institute, Stockholm, Sweden.
Brain Res Bull. 1988 Aug;21(2):257-63. doi: 10.1016/0361-9230(88)90240-7.
MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a parkinsonism-inducing dopamine (DA) neurotoxin most effective in primates. MPTP also causes a degeneration of both perikarya and axon terminals of the nigrostriatal DA neurons in C57 BL/6 mice. The time courses of the changes in tyrosine hydroxylase immunoreactive objects, endogenous DA concentrations and specifically bound 3H-mazindol as markers of the integrity of DA neurons were studied in substantia nigra and striatum of adult C57 BL/6 mice, after systemic treatment with MPTP or intranigral injections of the catecholamine neurotoxin 6-hydroxydopamine (6-OHDA). A rapid decrease in the three parameters studied was found in the substantia nigra during the first 2 days after MPTP-treatment while the MPTP-induced effects in the striatum were more protracted and maximal reduction was observed 7 days after MPTP. A basically similar pattern was found when studying the 6-OHDA-induced anterograde degeneration of the nigrostriatal system. These results indicate that in C57 BL/6 mice, MPTP primarily destroys the DAergic perikarya with a subsequent anterograde degeneration of the striatal axon terminals, although a limited rapid destruction of some striatal terminals cannot be excluded.
MPTP（1-甲基-4-苯基-1,2,3,6-四氢吡啶）是一种诱发帕金森综合征的多巴胺（DA）神经毒素，对灵长类动物最为有效。MPTP还会导致C57 BL/6小鼠黑质纹状体DA神经元的胞体和轴突终末发生退化。在用MPTP进行全身治疗或向黑质内注射儿茶酚胺神经毒素6-羟基多巴胺（6-OHDA）后，研究了成年C57 BL/6小鼠黑质和纹状体中酪氨酸羟化酶免疫反应性物质、内源性DA浓度以及作为DA神经元完整性标志物的特异性结合3H-吗茚酮的变化时间进程。在MPTP治疗后的头2天内，黑质中所研究的三个参数迅速下降，而MPTP对纹状体的影响更为持久，在MPTP治疗7天后观察到最大程度的降低。在研究6-OHDA诱导的黑质纹状体系统顺行性退变时发现了基本相似的模式。这些结果表明，在C57 BL/6小鼠中，MPTP主要破坏DA能胞体，随后纹状体轴突终末发生顺行性退变，尽管不能排除一些纹状体终末有限的快速破坏。
