Oral administration of semisynthetic sphingolipids promotes recovery of striatal dopamine concentrations in a murine model of parkinsonism.
The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administered to young C57/B16J black mice caused a striatal dopamine depletion that could be at least partially reversed by chronic intraperitoneal administration of GM1 ganglioside. The present study shows that the semisynthetic sphingolipids LIGA 4 (II3Neu-5-AcGgOse4-2-d-erythro-1,3-dihydroxy-2-acetamide-4-t rans-octadacene) and LIGA 20 (II3Neu-5-AcGgOse4-2-d-erythro-1,3-dihydroxy-2-chloro-acetam ide-4- trans-octadacene) are also effective in at least partially reversing MPTP-induced striatal dopamine depletions in mice after oral administration. These results suggest that semisynthetic ganglioside derivatives may be superior to the parent GM1 ganglioside for human clinical use.
Schneider
J S
JS
Department of Neurology, Hahnemann University School of Medicine, Philadelphia, PA 19102.
DiStefano
L
L
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005677:G(M1) Ganglioside / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009994:Osmolar Concentration; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000378:metabolism*; D013107:Sphingolipids / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000494:pharmacology; D013110:Sphingosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
C086917:LIGA 4; D013107:Sphingolipids; 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; D006719:Homovanillic Acid