Oligodendrocyte apoptosis mediated by caspase activation

Treatment with NGF causes long-term cultures of oligodendrocytes to die via a yet undefined mechanism mediated by the p75 neurotrophin receptor. The p 75 receptor belongs to the TNF receptor superfamily of molecules, which inc ludes Fas and p55 TNF receptors. The Fas and TNF receptors use adaptor mole cules to recruit and activate caspase-8 to the receptor. Using a combinatio n of immunohistochemical and Western blotting assays, we have examined casp ase activity during NGF-induced apoptosis. Interestingly, although caspase- 1 [interleukin-1 beta-converting enzyme (ICE)], caspase-2, caspase-3, and c aspase-8 were expressed in oligodendrocytes, only caspase-1, -2, and -3 wer e activated after NGF treatment, whereas caspase-8 was not. These data sugg est that the mechanism of apoptosis by NGF through the p75 receptor is diff erent from TNF and Fas-mediated killing. gamma Radiation of oligodendrocyte s also activated a similar subset of caspases as NGF, indicating that NGF-i nduced oligodendrocyte apoptosis uses a similar cell death execution mechan ism as injury models. This consolidates a potential role of the p75 neurotr ophin receptor during stress and inflammatory conditions.