Neuroprotection of brain-derived neurotrophic factor against hypoxic injury in vitro requires activation of extracellular signal-regulated kinase and phosphatidylinositol 3-kinase

Int J Dev Neurosci. 2008 May-Jun;26(3-4):363-70. doi: 10.1016/j.ijdevneu.2007.11.005. Epub 2007 Dec 17.


Intrauterine asphyxia is one of the major contributors for perinatal death, mental and physical disorders of surviving children. Brain-derived neurotrophic factor (BDNF) provides a promising solution to hypoxic injury due to its survival-promoting effects. In an attempt to identify possible molecular mechanisms underlying the neuroprotective role of BDNF, we studied extracellular signal-regulated kinase (ERK), phosphatidylinositol 3-kinase (PI-3-K) and p38 mitogen-activated protein kinase (MAPK) pathways. We demonstrated that BDNF protected cortical neurons against hypoxic injury in vitro via activation of both the ERK and PI-3-K pathways but not the p38 MAPK pathway. We also showed that both hypoxic stimuli and exogenous BDNF treatment phosphorylated the cyclic AMP response element-binding protein (CREB) and that CREB phosphorylation induced by BDNF was mediated via the ERK pathway in cultured cortical neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / enzymology*
  • Brain / physiopathology
  • Brain-Derived Neurotrophic Factor / pharmacology*
  • Cells, Cultured
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / enzymology
  • Cerebral Cortex / physiopathology
  • Cyclic AMP Response Element-Binding Protein / drug effects
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / pharmacology
  • Female
  • Fetal Hypoxia / enzymology*
  • Fetal Hypoxia / physiopathology
  • Hypoxia-Ischemia, Brain / drug therapy
  • Hypoxia-Ischemia, Brain / enzymology*
  • Hypoxia-Ischemia, Brain / physiopathology
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Neurons / drug effects
  • Neurons / enzymology
  • Neuroprotective Agents / pharmacology
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphorylation / drug effects
  • Pregnancy
  • Rats


  • Brain-Derived Neurotrophic Factor
  • Cyclic AMP Response Element-Binding Protein
  • Enzyme Inhibitors
  • Neuroprotective Agents
  • Phosphatidylinositol 3-Kinases
  • Mitogen-Activated Protein Kinase 3