LIGA 20 increases striatal dopamine levels in aged MPTP-treated mice refractory to GM1 ganglioside treatment.
Administration of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to aged (12 months) C57 black mice results in a striatal dopamine depletion that can be partially reversed only by long-term (i.e. 8 weeks) intraperitoneal administration of GM1 ganglioside. The present study shows that the semi-synthetic sphingolipid LIGA 20 (II3Neu5AcGgOse4-2-d-erythro-1,3-dihydroxy-2-dichloro-acetrylam ide-4- transoctadene) can partially reverse MPTP-induced striatal dopamine depletions in aged mice after being administered orally for only 4 weeks. GM1 ganglioside administered for 4 weeks had no effect on striatal dopamine levels. These results suggest that LIGA 20 is more potent than the parent GM1 ganglioside and may exert effects on the damaged nervous system under conditions in which GM1 is ineffective.
Schneider
J S
JS
Department of Neurology, Hahnemann University School of Medicine, Philadelphia, PA 19102.
DiStefano
L
L
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004351:Drug Resistance; D005677:G(M1) Ganglioside / Q000627:therapeutic use* / Q000031:analogs & derivatives; D020267:MPTP Poisoning; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010302:Parkinson Disease, Secondary / Q000188:drug therapy*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D000978:Antiparkinson Agents; D015102:3,4-Dihydroxyphenylacetic Acid; C086919:LIGA 20; D005677:G(M1) Ganglioside; D013110:Sphingosine; D004298:Dopamine