Bcl-xL protects cerebellar granule neurons against the late phase, but not against the early phase of glutamate-induced cell death

Neuronal death can take on many different forms, from well-defined apoptosis to caspase-independent processes. While members of the Bcl-2 family of intracellular proteins are known to be involved in classic apoptotic cascades, their role in necrosis has been less well defined. Here, we applied a cell-permeable form of the anti-apoptotic Bcl-2 family member Bcl-xL on glutamate-treated rat primary cerebellar granule neurons to test its effect on neuronal survival. Bcl-xL inhibited the late phase of cell death, when caspases are activated, but it did not inhibit the early, caspase-independent phase of cell death. These different phases of cell death following glutamate treatment have not been taken into account in many earlier reports either supporting or refuting an involvement of Bcl-2 family members in excitotoxic cell death. Our results suggest that under our experimental conditions, Bcl-xL inhibits caspase-dependent apoptosis, but not caspase-independent neuronal death.