Effects of ceramide analogs on myelinating organ cultures

Abstract

Analogs of ceramide which inhibit galactocerebrosidase also demyelinate or inhibit myelination in organ cultures of rat cerebellum. The potency of the analogs in culture correlated with their effectiveness as inhibitors of cerebrosidase, but not with their effectiveness as inhibitors of galactosyl transferase. The most effective compound was the decanoyl amide of 3-phenyl-2-amino-1,3-propanediol with erythro-conformation. Stimulators of cerebrosidase also demyelinated cultures. With both groups of compounds, myelin sheats became distorted, then broke into lipid droplets. Axons were preserved, but neurons showed some nuclear changes and granularity. Metabolic studies with the most effective inhibitor showed that glucose incorporation into cerebroside and other alkali-stable lipids was initially depressed compared to proteins and total lipids.