GM1 gangliosides alter acute MPTP-induced behavioral and neurochemical toxicity in mice.
We investigated the effect of GM1 gangliosides on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model of Parkinson disease. Five groups of mice (saline, GM1 (30 mg/kg), MPTP, MPTP + GM1 (15 mg/kg), MPTP + GM1 (30 mg/kg] were compared. GM1 was given daily via intraperitoneal injection before and during 13 daily doses of MPTP (30 mg/kg). Mice were tested for locomotion (1) within 2 h of an MPTP dose (to measure reduced motor activity), and (2) within 24 h of an MPTP dose (after animals had recovered and exhibited hyperactivity). We found that mice given GM1 gangliosides exhibited significantly less MPTP-induced behavior. This effect was most evident with the 15 mg/kg GM1 dose. GM1 also appeared to attenuate MPTP-induced neurochemical changes. GM1 effects indicating enhancement of DA turnover and preservation of DA, DOPAC and HVA concentrations in the striatum were found after the 8th MPTP dose. These latter neurochemical changes, however, were transient and not present after the 13th MPTP dose. Our data would suggest that gangliosides may reduce acute MPTP-induced neurotoxicity in mice either through an increase in DA neuron survival and/or the augmentation of striatal DA activity.
Fazzini
E
E
Department of Neurology, Boston University School of Medicine, MA.
Durso
R
R
Davoudi
H
H
Szabo
G K
GK
Albert
M L
ML
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D005677:G(M1) Ganglioside / Q000494:pharmacology* / Q000627:therapeutic use; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009068:Movement / Q000187:drug effects*; D010300:Parkinson Disease / Q000188:drug therapy*; D010302:Parkinson Disease, Secondary / Q000378:metabolism
D015102:3,4-Dihydroxyphenylacetic Acid; D005677:G(M1) Ganglioside; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine; D006719:Homovanillic Acid