Brain-derived neurotrophic factor protects rat cerebral cortical neurons from intermittent hypoxia in vitro

Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal survival and growth and participates in neuronal plasticity. BDNF binds to its high affinity receptor TrkB and activates signal transduction cascades crucial for the production of cyclic adenosine mono phosphate (cAMP)-response element binding protein (CREB), which contributes to neurotrophin-mediated survival in the central nervous system. This is accomplished by activating antiapoptotic gene expression and CREB Serine-133 (Ser133) phosphorylation, which is required for the activation of CREB-regulated transcription by neurotrophins. However, the specific mechanisms of BDNF-mediated neuroprotection in vitro remain not well understood. The aim of this study was to determine whether BDNF's neuroprotective effects on embryonic rat cortical neurons exposed to intermittent hypoxia involved CREB phosphorylation. We constructed an adenoviral vector encoding rat BDNF (Ad-BDNF) and performed an enzyme linked immunosorbent assay (ELISA) to measure the levels of BDNF and CREB. We also measured the viability of neurons transfected with BDNF in hypoxic culture conditions. We found that the levels of BDNF were significantly higher in neurons compared to control (P < 0.01). The neurons in the experimental groups transfected with BDNF were much more viable than those cultured under the hypoxic control conditions without BDNF. Hypoxia and BDNF both induced the phosphorylation of CREB in embryonic cortical neurons. This study suggests that BDNF may promote neuronal survival in intermittently hypoxic environments. Furthermore, the neuroprotective action of BDNF on embryonic rat cortical neurons exposed to intermittent hypoxia is partly mediated via CREB phosphorylation.