GM1 ganglioside partially rescues cultured dopaminergic neurons from MPP(+)-induced damage: dependence on initial damage and time of treatment.
GM1 ganglioside is believed to be important in promoting the recovery of neurons from injury. The present study assesses the ability of GM1 to repair or prevent the damage of dopamine neurons caused by the neurotoxin 1-methyl-4-phenylpyridinium (MPP+). Treatment of mesencephalic cell cultures with 2.5 microM MPP+ resulted in the loss of 30% of tyrosine hydroxylase (TH) immunoreactive neurons. In contrast, cultures administered 100 microM GM1 ganglioside for 3 days after toxin treatment contained nearly control numbers of TH+ neurons (97%). This reparative effect of GM1 was reflected in parallel increases in TH enzyme activity, dopamine and dopac levels. Cultures sustaining greater insult from higher doses of MPP+ (5.0-10.0 microM) did not benefit from ganglioside treatment, suggesting that rescue by GM1 depended on the degree of initial damage to cells. Moreover, the timing of ganglioside treatment was critical; pretreatment with GM1 alone did not prevent or attenuate the damage caused by subsequent incubation in 2.5 microM MPP+.
Stull
N D
ND
Department of Neurology, Hahnemann University, Philadelphia, PA 19102.
Schneider
J S
JS
Iacovitti
L
L
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000166:cytology; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D007150:Immunohistochemistry; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011726:Pyridinium Compounds / Q000037:antagonists & inhibitors* / Q000633:toxicity; D051381:Rats; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis / Q000378:metabolism
D011726:Pyridinium Compounds; D015102:3,4-Dihydroxyphenylacetic Acid; D005677:G(M1) Ganglioside; C026560:1-(4-methoxyphenyl)pyridinium; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine