Cellular levels of TrkB and MAPK in the neuroprotective role of BDNF for embryonic rat cortical neurons against hypoxia in vitro.
Intrauterine asphyxia often results in neonatal loss or mental retardation. Brain-derived neurotrophic factor (BDNF) has been shown to be a protective agent against hypoxic damage to neurons. To understand the signaling mechanism underling the neuroprotective function of BDNF and to find therapeutic interventions for intrauterine asphyxia, we utilized an immunofluorescent technique to measure the intracellular levels of tyrosine kinase B (TrkB), phosphorylated TrkB, and the mitogen-activated protein kinase (MAPK) in the rat embryonic cortical neurons cultured in hypoxic conditions with and without BDNF pretreatment. The results showed that the fluorescent intensity of TrkB and phosphorylated TrkB in the cytoplasm and the fluorescent intensity of MARK in both cytoplasma and nucleus of the neurons were significantly increased in the presence of BDNF. The results indicate that the neuroprotective function of BDNF against hypoxia-induced neurotoxicity requires the participation of TrkB and is transduced via the Ras-MAPK signaling pathway.
Meng
Mao
M
Department of Pediatrics, West China Second University Hospital, Sichuan University, 20 Renmin Nanlu, Chengdu Sichuan 610041, PR China.
Zhiling
Wang
W
Hui
Zhou
Z
Shengfu
Li
L
Dan
Yu
Y
Jiping
Hua
H
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology; D005311:Fetal Hypoxia / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D005455:Fluorescent Antibody Technique; D002534:Hypoxia, Brain / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects / Q000378:metabolism*; D009410:Nerve Degeneration / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D020813:Receptor, trkB; D019950:Mitogen-Activated Protein Kinase 1