单唾液酸神经节苷脂(GM_1)对经MPTP破坏的小鼠黑质纹状体多巴胺神经元的保护作用

将1一甲基一4苯基一1.2.3.6四氢吡啶(MPTP)经腹腔注入小鼠,连续注射6天,一组动物注射后次日处死;另一组动物存活二周后处死;第三组动物在给予1—甲基一4苯基一1.2.3.6四氢吡啶的同时,经腹膜腔注射神经节苷脂持续三周;第四组为对照组.各组动物脑用酪氨酸羟化酶抗体进行免疫组化观察.结果发现1一甲基一4苯基一1.2.3.6四氢吡啶连续注射后次日处死的动物黑质致密部酪氨酸羟化酶阳性神经元数量明显减少,纹状体中酪氨酸羟化酶阳性终末亦明显稀疏.损害后存活二周组,不论黑质或纹状体的损害均略轻.单唾液酸神经节苷脂组黑质致密部酪氨酸羟化酶阳性神经元及纹状体中酪氨酸羟化酶阳性终末均较上两组明显增多.实验表明,单唾液酸神经节苷脂对经1一甲基一4苯基一1.2.3.6四氢吡啶破坏后的小鼠黑质纹状体系多巴胺神经元有保护作用,防止多巴胺神经元因损害引起的继发性退变.

THE EFFECT OF GANGLIOSIDE GM, ON MPTP TREATED MICE

The effect of ganglioside GM1 on recovery of the dopaminergic nigrostriatal system in the brain of MPTP-treated mice were studied. Intraperitoneal injections of l-methyl-4-phenyl-1,2,3,6-tetrhydropyridine (MPTP) were given to mice 20 mg/kg twice a day for 6 days. Mice in Group 1 were sacrificed one day after the last injection. In Group 2 mice were sacrificed two weeks after the last injdection. In Group 3 ganglioside GM1 was injected 30 mg/kg ip. immediatelly before the first MPTP injection, and then once a day for 3 weeks. Group 4 was used as control group injected with saline. Tyrosine hydroxylase immunocytochemistry revealed that the injection of MPTP resulted in the marked reduction of TH positive cells in the striatum in mice one day after MPTP treatment, and the partial reduction of TH positive cells in the substantia nigra and the partial recovery of TH-IR fibers in the substantia nigra and the partial recovery of TH-IR fibers in the striatum of mice two weeks after MPTP treatment. Administration of ganglisoside GM1 to MPTP treated mice enhanced reappearane of striatal TH-IR fiber and reduced the lose of TH positive cells in the substantia nigra part. The results suggest that ganglioside GM1 may stimulate sprouting or protect neurons of the nigrostriatal dopaminergic system from secondary degenerative changes after MPTP injury.