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

Xiaomei Sun; Hui Zhou; Xiaoli Luo; Shengfu Li; Dan Yu; Jiping Hua; Dezhi Mu; Meng Mao

doi:10.1016/j.ijdevneu.2007.11.005

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.

Authors

Xiaomei Sun¹, Hui Zhou, Xiaoli Luo, Shengfu Li, Dan Yu, Jiping Hua, Dezhi Mu, Meng Mao

Affiliation

¹ Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, PR China.

PMID: 18243629
DOI: 10.1016/j.ijdevneu.2007.11.005

Abstract

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

Substances

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