BDNF and NT-3 but not CNTF counteract the Ca2+ ionophore-induced apoptosisof cultured cortical neurons: involvement of dual pathways

The effect of neurotrophic factors on apoptosis induced by ionomycin, a pot ent Ca2+ ionophore, was investigated using cultured cortical neurons from e mbryonic rats. Brain-derived neurotophic factor (BDNF) and neurotrophin-3 ( NT-3) prevented the ionomycin-mediated cell death in a dose-dependent manne r. In contrast to the neurotrophins, cilliary neurotrophic factor (CNTF) di d not rescue neurons from cell death induced by ionomycin. The protective e ffect of BDNF was partially blocked by wortmannin, a phosphatidylinositol 3 -kinase inhibitor, and by PD98059, a MAP kinase kinase inhibitor. However, the addition of both compounds together completely inhibited the survival p romoting effect of BDNF. These results suggest that the neuroprotective eff ect of BDNF requires activation of both phosphatidylinositol-3 kinase and t he Ras/MAP kinase cascade and that CNTF signaling through other pathways is without an effect in this system. (C) 1999 Elsevier Science Ltd. All right s reserved.