Brain-Derived Neurotrophic Factor-Mediated Neuroprotection of Adult Rat Retinal Ganglion Cells In Vivo Does Not Exclusively Depend on Phosphatidyl-Inositol-3′-Kinase/Protein Kinase B Signaling

摘要: The neurotrophin brain-derived neurotrophic factor (BDNF) serves as a survival, mitogenic, and differentiation in both the developing adult CNS PNS. In an attempt to identify molecular mechanisms underlying BDNF neuroprotection, we studied activation of two potentially neuroprotective signal transduction pathways by trauma model. Transection optic nerve (ON) rat induces secondary death retinal ganglion cells (RGCs). Repeated intraocular injections prevent degeneration RGCs 14 d after ON lesion most likely inhibition apoptosis. Here, report that activates protein kinase B (PKB) via phosphatidyl-inositol-3'-kinase (PI-3-K)-dependent mechanism mitogen-activated kinases extracellular signal-regulated 1 (ERK1) ERK2. Furthermore, provide evidence suppresses cleavage enzymatic activity neuronal cell effector caspase-3. Distinct from our recent study which PI-3-K/PKB pathway attenuated survival-promoting action insulin-like growth factor-I on axotomized (Kermer et al., 2000), it does not case BDNF. Thus, assume depend single exerting its effects lesioned neurons.