Neuroprotective effect of brain-derived neurotrophic factor mediated by autophagy through the PI3K/Akt/mTOR pathway.
Brain‑derived neurotrophic factor (BDNF) has been demonstrated to be a potent growth factor that is beneficial in neuronal functions following hypoxia‑ischemia (HI). Mature BDNF triggers three enzymes, mitogen‑activated protein kinase (MAPK), phosphatidylinositol 3‑kinase (PI3K) and phosphoinositide phospholipase C-γ (PLCγ), which are its predominant downstream regulators. The PI3K‑Akt signaling pathway is upstream of the mammalian target of rapamycin (mTOR), which is important in the induction of autophagy. However, whether the neuroprotective effect of BDNF is mediated by autophagy through the PI3K/Akt/mTOR pathway remains to be elucidated. Cortical neurons were cultured following isolation from pregnant rats (gestational days 16‑18). The induction of autophagy following BDNF treatment was analyzed by microtubule‑associated protein light chain 3 (LC3) conversion and autophagosome formation. The phosphorylation of Akt, mTOR and ribosomal protein S6 kinase (p70S6K) was analyzed in cultured cells with or without BDNF treatment. Cell viability was determined by a Cell Counting Kit‑8 for estimating the protective effect of BDNF. Results demonstrated that autophagy was induced in cells with oxygen deprivation. BDNF promoted cell viability via the upregulation of autophagy. Moreover, LC3 upregulation was related to Akt/mTOR/p70S6K inhibition by BDNF. In conclusion, the results suggested that the neuroprotective effect of BDNF was mediated by autophagy through the PI3K/Akt/mTOR pathway.
Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
Ai
A
Chen
Li-Jing
LJ
Xiong
Yu
Y
Tong
Meng
M
Mao
D000818:Animals; D001343:Autophagy; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology / Q000502:physiology*; D015687:Cell Hypoxia; D002470:Cell Survival; D002478:Cells, Cultured; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D061251:Primary Cell Culture; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015854:Up-Regulation
D019208:Brain-Derived Neurotrophic Factor; D008869:Microtubule-Associated Proteins; D018696:Neuroprotective Agents; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; C526109:Anxa3 protein, rat; C546845:mTOR protein, rat