Differential accumulation of gangliosides by the brains of MPTP-lesioned mice.
Although gangliosides have been reported to enhance recovery from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced lesions of the substantia nigra, evidence as to whether the administered gangliosides actually reach this or any other site of lesion in the central nervous system (CNS) at which they putatively enhance recovery is lacking. Therefore, studies were carried out to determine the amount of 3H-labeled ganglioside that was accumulated by the brains of MPTP-treated mice as well as by brains of control mice. No significant difference in the accumulation of 3H-bovine brain gangliosides or 3H-GD1a was seen between lesioned and control brains up to 240 min after injection of the labeled lipids. However, significantly more label was associated with the brains of MPTP-treated mice compared to controls 120 and 240 min after the injection of 3H-GM1. Analysis of the lipids extracted from the brain of a 3H-GM1-treated mouse revealed that the majority of label was still associated with 3H-GM1, 240 min after its administration. Autoradiography of tissue sections from the brains of MPTP-treated mice injected with 3H-GM1 showed that label was present in the ventricular spaces of the brain. This observation suggests that the administered gangliosides are present in the cerebrospinal fluid, which indicates that they have the potential to reach the lesioned CNS site at which they putatively enhance recovery.
Saulino
M F
MF
Department of Biological Chemistry, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
Schengrund
C L
CL
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002417:Cattle; D002855:Chromatography, Thin Layer; D004298:Dopamine / Q000378:metabolism; D005677:G(M1) Ganglioside / Q000378:metabolism; D005732:Gangliosides / Q000378:metabolism*; D008297:Male; D051379:Mice; D012701:Serotonin / Q000378:metabolism
D005732:Gangliosides; C021298:ganglioside, GD1a; D012701:Serotonin; D005677:G(M1) Ganglioside; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine