PMID- 23942837
OWN - NLM
STAT- MEDLINE
DCOM- 20140317
LR  - 20220408
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Linking)
VI  - 8
IP  - 4
DP  - 2013 Oct
TI  - Neuroprotective effect of brain-derived neurotrophic factor mediated by autophagy 
      through the PI3K/Akt/mTOR pathway.
PG  - 1011-6
LID - 10.3892/mmr.2013.1628 [doi]
AB  - 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-gamma (PLCgamma), 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.
FAU - Chen, Ai
AU  - Chen A
AD  - Department of Pediatrics, West China Second University Hospital, Sichuan 
      University, Chengdu, Sichuan 610041, P.R. China.
FAU - Xiong, Li-Jing
AU  - Xiong LJ
FAU - Tong, Yu
AU  - Tong Y
FAU - Mao, Meng
AU  - Mao M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130813
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (LC3 protein, rat)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Neuroprotective Agents)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - *Autophagy
MH  - Brain-Derived Neurotrophic Factor/pharmacology/*physiology
MH  - Cell Hypoxia
MH  - Cell Survival
MH  - Cells, Cultured
MH  - Microtubule-Associated Proteins/metabolism
MH  - Neurons/*physiology
MH  - Neuroprotective Agents/pharmacology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Primary Cell Culture
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Rats, Sprague-Dawley
MH  - *Signal Transduction
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/metabolism
MH  - Up-Regulation
EDAT- 2013/08/15 06:00
MHDA- 2014/03/19 06:00
CRDT- 2013/08/15 06:00
PHST- 2013/03/17 00:00 [received]
PHST- 2013/07/03 00:00 [accepted]
PHST- 2013/08/15 06:00 [entrez]
PHST- 2013/08/15 06:00 [pubmed]
PHST- 2014/03/19 06:00 [medline]
AID - 10.3892/mmr.2013.1628 [doi]
PST - ppublish
SO  - Mol Med Rep. 2013 Oct;8(4):1011-6. doi: 10.3892/mmr.2013.1628. Epub 2013 Aug 13.