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.
Department of Neurobiology and Anatomy, University of Rochester School of Medicine, New York.
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D000375:Aging / Q000502:physiology*; D000818:Animals; D001921:Brain; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D004298:Dopamine / Q000502:physiology*; D005732:Gangliosides / Q000008:administration & dosage / Q000494:pharmacology*; D007150:Immunohistochemistry; D007267:Injections; D020267:MPTP Poisoning; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009416:Nerve Regeneration / Q000187:drug effects; D013238:Stereotaxic Techniques; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D005732:Gangliosides; C021298:ganglioside, GD1a; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine