Significance of gangliosides in neuronal differentiation of neuroblastoma cells and neurite growth in tissue culture

Addition of DL-threo-1-phenyl-2-decanolylamine-3-morpholino-1-propanol HCl (PDMP; 7-24 mu M) or Fumonisin B-1 (FB1; 30-50 mu M) to SH-SY5Y(trk-A) human neuroblastoma cells results within 4 days in a 40% decrease of the ganglioside content and in a reduction of nerve-growth-factor (NGF) -induced outgrowth of neuritic processes. NGF-induced enhancement of GAP-43 expression was not affected. However, unlike controls, immunostained GAP-43 appeared concentrated in defined areas of cell perikarya and mostly absent from cell processes. Presence of 20-mu M exogenous GM1 for 4 days in NGF and PDMP containing cell cultures led to an increase of cell-associated GM1 (15-fold), GM2 (10-fold), GM3 (15-fold), GD1a (4-fold), GD2, GD1b, and GT1b (all 3-fold), and partially reversed the PDMP (and FB1) effects on neurite growth and GAP-43 distribution. In a newly developed neuronal tissue culture system, PDMP and FB1 led to a comparable dose-dependent inhibition of neurite outgrowth from embryonic chicken spinal cord explants, which had been embedded into a fibrin matrix, In this system, addition of GM1 led to a further inhibition of neurite growth, probably due to an interaction with growth-promoting components present in the surrounding fibrin matrix.