Ceramide can induce cell death in sensory neurons, whereas ceramide analogues and sphingosine promote survival.

Ceramide has been shown to induce apoptosis in leukaemic cells and some other cell types, but there are few data on its role in neuronal cells. We investigated the effect of ceramide and its analogues in cultured sensory neurons from neonatal mice. These cells undergo apoptosis in the absence of neurotrophins. Treatment with ceramide or its analogues increased survival, both in the presence and absence of NGF. Sphingosine treatment also increased survival. In the presence of the ceramidase inhibitor N-oleoyl ethanolamine, which blocks conversion of ceramide to sphingosine, the addition of natural ceramide-induced cell death, even in the presence of nerve growth factor (NGF). N-oleoyl ethanolamine did not cause cell death by itself. N-oleoyl ethanolamine did not alter the response to ceramide analogues, indicating that they were not ceramidase substrates. These results indicate that, in sensory neurons, exogenous ceramide is converted to sphingosine, which promotes cell survival. When conversion is blocked by ceramidase inhibition, exogenous ceramide causes cell death, presumably due to the high levels of ceramide itself. The ceramide analogues all mimicked the effect of sphingosine rather than ceramide, casting serious doubt on their validity as models of ceramide action. Ceramide analogues could prevent neuronal death even in the combined presence of N-oleoyl ethanolamine and natural ceramide. Surprisingly, dihydro C2-ceramide, which is frequently used as a control for C2-ceramide, had the same effect as ceramide analogues.