Response of the damaged dopamine system to GM1 and semisynthetic gangliosides: effects of dose and extent of lesion.
GM1 ganglioside, administered to young C57/B16J mice with moderate (approx 85%) 1-methyl-4-phenyl-1,2,3,6-terahydropyridine (MPTP)-induced striatal dopamine depletions, caused a dose-dependent increase in striatal dopamine levels. This effect was maximal between 7.0 and 30.0 mg/kg and was not apparent at higher and lower doses of GM1. GM1 ganglioside treatment had no effect on striatal dopamine levels in mice with more extensive lesions of the dopamine system (i.e. approx 93% loss of striatal dopamine). The semisynthetic ganglioside derivative LIGA 20, administered orally, also increased striatal dopamine levels in moderately lesioned animals, albeit at lower doses than GM1. LIGA 20 administration also resulted in increased striatal dopamine levels in animals with more extensive dopamine lesions, where GM1 had no effect. These results show that both GM1 and its semisynthetic derivative LIGA 20 can partially restore striatal dopamine levels in MPTP-treated mice and that LIGA 20 is more potent and not subject to the same dose-limiting effects as GM1.
Schneider
J S
JS
Center for Neurological Research, Hahnemann University, Philadelphia, PA 19102, USA.
Distefano
L
L
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005677:G(M1) Ganglioside / Q000031:analogs & derivatives / Q000494:pharmacology; D005732:Gangliosides / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology
D000978:Antiparkinson Agents; D005732:Gangliosides; D015102:3,4-Dihydroxyphenylacetic Acid; C086919:LIGA 20; D005677:G(M1) Ganglioside; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D013110:Sphingosine; D004298:Dopamine