Exogenous GM₁ gangliosides induce partial recovery of the nigrostriatal dopaminergic system in MPTP-treated young mice but not in aging mice

The administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to young (2-3 months) and aging (12 months) C57BL 6 mice (4 × 20 mg/kg, i.p., given 12 h apart) reduced tyrosine hydroxylase (TH)-immunoreactive (IR) fibers in the striatum, and reduced dopamine (DA) concentration to 28% of controls in young, and 16% of controls in aging mouse brain five weeks after administration. Although GM₁ ganglioside treatment (30 mg/kg, i.p., daily for 5 weeks) restored striatal dopamine concentration to 74% of the control concentration in young mice, such an apparent recovery was not seen in aging brain. Immunocytochemical analysis also showed marked recovery of TH-IR fibers in the striatum of MPTP-depleted young mice treated with GM₁ ganglioside while TH-IR fibers in the striatum of MPTP-depleted aging mice showed no recovery with such treatment. We conclude that treatment of MPTP-depleted young mice with GM₁ ganglioside results in partial recovery in the striatal DA system, but such benefits do not extend to aging mice.