MPTP-induced parkinsonism: acceleration of biochemical and behavioral recovery by GM1 ganglioside treatment.
The effects of GM1 ganglioside administration on functional recovery and recovery of caudate nucleus dopamine levels have been assessed in cats made parkinsonian by administration of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Cats made severely parkinsonian by MPTP administration began to show spontaneous functional recovery by the third week after MPTP, as had been observed in previous studies with this model. In contrast, cats with similar initial impairment but which received 3 weeks of GM1 ganglioside treatment (30 mg/kg, i.p. daily) showed an accelerated behavioral recovery, showing significant functional improvement after the first week of GM1 treatment and almost normal function by the end of the third week of treatment. The GM1-treated cats had caudate nucleus dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), and HVA levels significantly increased above levels measured in saline-treated MPTP control cats. A second group of cats received MPTP only until the first signs of parkinsonism were observed and thus overall had a less severe initial syndrome than the cats described previously. Again, while all cats showed functional recovery over time, the recovery process was accelerated in GM1-treated cats. GM1 treatment also caused a significant increase in caudate dopamine levels in these cats. These results suggest that GM1 ganglioside administration can result in increased dopamine levels even in the heavily denervated striatum and accelerate functional recovery after an MPTP-induced lesion of the nigrostriatal dopamine system in the cat. This suggests that GM1 or other trophic factor therapies may be fruitful treatment strategies for a disorder of nigrostriatal function such as Parkinson's disease.
Schneider
J S
JS
Department of Neurology, Hahnemann University School of Medicine, Philadelphia, PA 19102.
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002415:Cats; D002421:Caudate Nucleus / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D005260:Female; D005677:G(M1) Ganglioside / Q000494:pharmacology / Q000627:therapeutic use*; D006719:Homovanillic Acid / Q000378:metabolism; D020267:MPTP Poisoning; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology
D015102:3,4-Dihydroxyphenylacetic Acid; D005677:G(M1) Ganglioside; D004298:Dopamine; D006719:Homovanillic Acid