BDNF and NT-3 but not CNTF counteract the Ca super(2+) ionophore-induced apoptosis of cultured cortical neurons: involvement of dual pathways

• Published in: Neuropharmacology Vol. 38; no. 2; pp. 283 - 288
• Main Authors: Takei, Nobuyuki, Tanaka, Osamu, Endo, Yasuhisa, Lindholm, D, Hatanaka, Hiroshi
• Format: Journal Article
• Language: English
• Published: 01.02.1999
• ISSN: 0028-3908

The effect of neurotrophic factors on apoptosis induced by ionomycin, a potent Ca super(2+) ionophore, was investigated using cultured cortical neurons from embryonic rats. Brain-derived neurotophic factor (BDNF) and neurotrophin-3 (NT-3) prevented the ionomycin-mediated cell death in a dose-dependent manner. In contrast to the neurotrophins, cilliary neurotrophic factor (CNTF) did not rescue neurons from cell death induced by ionomycin. The protective effect 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 promoting effect of BDNF. These results suggest that the neuroprotective effect of BDNF requires activation of both phosphatidylinositol-3 kinase and the Ras/MAP kinase cascade and that CNTF signaling through other pathways is without an effect in this system.