Date I, Notter M F, Felten S Y, Felten D L
Department of Neurobiology and Anatomy, University of Rochester School of Medicine, New York.
J Neurosci Res. 1991 Apr;28(4):525-30. doi: 10.1002/jnr.490280409.
The systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to young (2 months old) and aging (12 months old) C57BL/6 mice (4 x 20 mg/kg i.p. given 12 hr apart) reduced tyrosine hydroxylase (TH)-immunoreactive (IR) fibers in the striatum and reduced dopamine (DA) concentration to 35% of controls in young and 22% of controls in aging mouse brain 5 weeks after administration. Stereotaxic injection of GD1a ganglioside (3 x 100 micrograms, 5 days apart) into the striatum of MPTP-treated young mice restored striatal DA concentration to 52% of the control concentration 5 weeks after MPTP injection. Similar injections of GD1a ganglioside restored striatal DA concentration of MPTP-treated aging mice to only 31% of the control concentration. Immunocytochemical analysis showed significant recovery of TH-IR fibers in the striatum of MPTP-depleted young mice treated with GD1a ganglioside, while TH-IR fibers in the striatum of MPTP-depleted aging mice treated with GD1a ganglioside showed less recovery. We conclude that treatment of MPTP-depleted aging mice with GD1a ganglioside results in more limited recovery in the nigrostriatal DA system than in young mice.
给年轻（2个月大）和老龄（12个月大）的C57BL/6小鼠腹腔注射1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）（4×20mg/kg，间隔12小时给药），5周后，年轻小鼠纹状体中酪氨酸羟化酶（TH）免疫反应性（IR）纤维减少，多巴胺（DA）浓度降至对照组的35%；老龄小鼠脑内DA浓度降至对照组的22%。对MPTP处理后的年轻小鼠纹状体进行立体定位注射GD1a神经节苷脂（3×100微克，间隔5天），MPTP注射5周后，纹状体DA浓度恢复至对照浓度的52%。对MPTP处理后的老龄小鼠进行类似注射，纹状体DA浓度仅恢复至对照浓度的31%。免疫细胞化学分析显示，用GD1a神经节苷脂处理的MPTP损伤年轻小鼠纹状体中TH-IR纤维有显著恢复，而用GD1a神经节苷脂处理的MPTP损伤老龄小鼠纹状体中TH-IR纤维的恢复较少。我们得出结论，与年轻小鼠相比，用GD1a神经节苷脂治疗MPTP损伤的老龄小鼠，黑质纹状体DA系统的恢复更有限。
