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 x 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.
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Department of Neurobiology and Anatomy, University of Rochester School of Medicine, NY 14642.
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D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000375:Aging / Q000378:metabolism*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*
D005677:G(M1) Ganglioside; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine