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Central glial and neuronal populations display differential sensitivity to ceramide-dependent cell death
P Casaccia-Bonnefil1, L Aibel, M V Chao
1Department of Cell Biology and Anatomy, Cornell University Medical College, New York, New York, 10021 USA.
Abstract:
Ceramide is a lipid second messenger implicated in the mechanism of apoptotic cell death. The effect of the cell-permeable ceramide analogue C2 has been tested on primary cortical cultures of neurons, astrocytes, and oligodendrocytes as well as on the bipotential glial precursor cell line CG-4. After 24 hr of treatment, C2 ceramide induced a dose-dependent cell death in primary oligodendrocytes and precursor cells, with a maximum effect at 10 microM. Commitment of oligodendrocytes to cell 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 condensation. In contrast, similar treatment of primary neuronal or astrocytic cortical cultures had no effect on cell survival. Neurons and astrocytes were resistant to 10 microM C2 ceramide. Furthermore, bipotential progenitors that were differentiated toward astrocytes also became resistant to ceramide treatment as they acquired a mature astrocytic phenotype. These experiments suggest that cell type specific factors are required for ceramide-mediated cell death in the nervous system.
Insights
Ceramide analogue C2 induces cell death in oligodendrocytes and glial precursors but not neurons or astrocytes. This suggests specific cellular factors are necessary for ceramide-mediated apoptosis in the nervous system.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Ceramide acts as a lipid second messenger in apoptotic cell death pathways.
- Understanding ceramide's role in neural cell death is crucial for neurodegenerative disease research.
Purpose of the Study:
- To investigate the effects of a cell-permeable ceramide analogue (C2) on different neural cell types.
- To determine the cell-type specificity of ceramide-induced apoptosis in the central nervous system.
Main Methods:
- Treatment of primary cortical cultures (neurons, astrocytes, oligodendrocytes) and CG-4 glial precursor cells with C2 ceramide.
- Dose-dependent analysis of cell death.
- Ultramicroscopic examination of cellular morphology.
Main Results:
- C2 ceramide caused dose-dependent cell death in primary oligodendrocytes and CG-4 cells (max effect at 10 µM).
- Oligodendrocyte cell death commitment occurred within 6 hours, characterized by membrane blebbing.
- Neurons and astrocytes exhibited resistance to C2 ceramide, even at 10 µM.
- Differentiated astrocytes and mature neuronal/astrocytic cultures were resistant to ceramide.
Conclusions:
- Ceramide-mediated cell death in the nervous system is cell-type specific.
- Oligodendrocytes and glial precursors are particularly vulnerable to ceramide-induced apoptosis.
- Mature neurons and astrocytes possess resistance mechanisms against ceramide toxicity.