Gangliosides modulate Schwann cell proliferation and morphology

We examined the effect of gangliosides on Schwann cell cultures isolated from neonatal rat sciatic nerves. Addition of gangliosides (GM1, GM3, and ganglioside mixture) at concentrations between 0.25 and 2 mg/ml significantly diminished both the baseline rate of proliferation of the Schwann cells and their response to two types of mitogens, the axolemmal fragments and derivatives of adenosine 3'-5'-monophosphate (cAMP). Gangliosides, the sialic acid residue of which had been removed, were highly toxic to the Schwann cells, which went to indicate that sialic acid is necessary to produce the inhibitory effects. Gangliosides also produced prominent changes in the morphological appearance of the Schwann cells. Most of the Schwann cells treated with gangliosides had an elongated shape with long processes and an alignment of end-to-end or side-by-side cell adhesion. These effects of gangliosides apparently were not mediated by cAMP, since intracellular cyclic adenosine monophosphate (cAMP) of Schwann cells at a basal- and forskolin-stimulated level was not altered by the exogenous gangliosides. These findings indicate that the direct effect of gangliosides on Schwann cells should also be considered as a background mechanism of ganglioside-induced facilitation of neuronal regeneration.