Stereotaxic injection of GD1a ganglioside induces limited recovery of striatal dopaminergic system in MPTP-treated aging mice.

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.