CENTRAL GLIAL AND NEURONAL POPULATIONS DISPLAY DIFFERENTIAL SENSITIVITY TO CERAMIDE-DEPENDENT CELL-DEATH

Ceramide is a lipid second messenger implicated in the mechanism of ap optotic cell death, The effect of the cell-permeable ceramide analogue C2 has been tested on primary cortical cultures of neurons, astrocyte s, and oligodendrocytes as well as on the bipotential glial precursor cell line CG-4, After 24 hr of treatment, C2 ceramide induced a dose-d ependent cell death in primary oligodendrocytes and precursor cells, w ith a maximum effect at 10 mu M. Commitment of oligodendrocytes to cel l death occurred within the first 6 hr of treatment, Ultramicroscopic analysis of primary oligodendrocytes exposed to C2 ceramide for 3.5 hr revealed extensive membrane blebbing in the absence of nuclear conden sation, In contrast, similar treatment of primary neuronal or astrocyt ic cortical cultures had no effect on cell survival, Neurons and astro cytes were resistant to 10 mu M C2 ceramide, Furthermore, bipotential progenitors that were differentiated toward astrocytes also became res istant to ceramide treatment as they acquired a mature astrocytic phen otype, These experiments suggest that cell type specific factors are r equired for ceramide-mediated cell death in the nervous system. (C) 19 96 Wiley-Liss, Inc.