Metabolism of exogenous gangliosides in cerebellar granule cells, differentiated in culture.

The metabolism of exogenous gangliosides in the CNS has been investigated using cerebellar granule cells in culture as a model. For this purpose, GM2 and GM1, both isotopically radiolabeled at the level of the terminal sugar residue or of the long chain base moiety, were administered to differentiated cells for a 15-h pulse, and their metabolic fate was followed in a time course protocol. At each time investigated (1, 2, and 4 days after the pulse), several compounds, besides the ones administered, were detected: (a) GM2 (only after GM1 was given), GM3, lactosylceramide, glucosylceramide, and ceramide, all products of ganglioside stepwise catabolism; (b) GM1 (only after GM2 was given), GD1a, GD1b, O-Ac-GT1b, and GT1b, that is, gangliosides more complex than the one administered; and (c) sphingomyelin. The compounds derived from ganglioside catabolism and sphingomyelin were detected only after administration of long chain base-labeled precursors, whereas the others were found regardless of the labeling position of the precursor. In addition, radioactivity was incorporated in the delipidized residue when sugar-labeled gangliosides were given to cells. Besides qualitative differences, quantitative ones were found after administration of the different precursors.(ABSTRACT TRUNCATED AT 250 WORDS)