Ceramide selectively inhibits apoptosis-associated events in NGF-deprived sympathetic neurons

Ceramide manifests both neurotoxic and neuroprotective properties depending on the experimental system. Ito and Horigome previously reported that cera mide delays apoptosis in a classic model of developmental programmed cell d eath, i.e, sympathetic neurons undergoing NGF deprivation.(1) Here, we inve stigated the actions of ceramide upon the biochemical and genetic changes t hat occur in NGF deprived neurons. We correlate ceramide's neuroprotective actions with the ability of ceramide to antagonize NGF deprivation-induced oxidative stress and c-jun induction, both of which contribute to apoptosis in this model. However, ceramide did not block NGF deprivation-induced dec lines in RNA and protein synthesis, suggesting that ceramide does not slow all apoptosis-related events. Overall, these results are significant in tha t they show that ceramide acts early in the death cascade to antagonize two events necessary for NGF-deprivation induced neuronal apoptosis, Moreover, these results dissociate declines in neuronal function, i.e. macromolecula r synthesis, from the neuronal death cascade.