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 × 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 GDla ganglioside (3 × 100 μg, 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 GDla 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 treatedwith GDla ganglioside, while TH‐IR fibers in the striatum of MPTP‐depleted aging mice treated with GDla ganglioside showed less recovery. We conclude that treatment of MPTP‐deleted again mice with GD1a ganglioside results in more limited recovery in the nigrostriatal DA system than in young mice.