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/Bl6J black; mice caused a striatal dopamine depletion that could be at least partially reversed by chronic intraperitoneal administration of GM, ganglioside. The present study shows that the semisynthetic sphingolipids LIGA 4 (II(3)Neu-5-AcGgOse(4)-2-d-erythro-1,3 -dihydroxy-2-acetamide-4-trans-octadacene) and LIGA 20 (II(3)Neu-5-AcGgOse(4)-2-d-erytkro-1,3-dihydroxy-2-chloro-acetamide-acetamide-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 GM, ganglioside for human clinical use.