PMID- 30365051
OWN - NLM
STAT- MEDLINE
DCOM- 20190305
LR  - 20190305
IS  - 1791-244X (Electronic)
IS  - 1107-3756 (Print)
IS  - 1107-3756 (Linking)
VI  - 43
IP  - 1
DP  - 2019 Jan
TI  - Brain-derived neurotrophic factor inhibits hyperglycemia-induced apoptosis and 
      downregulation of synaptic plasticity-related proteins in hippocampal neurons via 
      the PI3K/Akt pathway.
PG  - 294-304
LID - 10.3892/ijmm.2018.3933 [doi]
AB  - It is not known whether brain‑derived neurotrophic factor (BDNF) protects 
      hippocampal neurons from high glucose‑induced apoptosis and/or synaptic 
      plasticity dysfunction. The present study aimed to assess whether BDNF exerted a 
      neuroprotective effect in rat hippocampal neurons exposed to high glucose and 
      examine the underlying mechanisms. The apoptosis of primary hippocampal neurons 
      was assessed by Annexin V‑fluorescein isothiocyanate/propidium iodide staining. 
      The mRNA and protein expression levels were measured by reverse 
      transcription‑-quantitative polymerase chain reaction and western blot 
      experiments, respectively. Synaptic plasticity was evaluated by the 
      immunolocalization of synaptophysin (Syn). Exposure of the hippocampal neurons to 
      high glucose (75 mM for 72 h) resulted in cell apoptosis, decreased mRNA and 
      protein expression levels of three synaptic plasticity‑related proteins (Syn, Arc 
      and cyclic AMP response element‑binding protein), and changes in the cellular 
      distribution of Syn, indicating loss of synaptic density. These effects of high 
      glucose were partially or completely reversed by prior administration of BDNF 
      (50 ng/ml for 24 h). Pre‑treatment with wortmannin, a 
      phosphatidylinositol‑3‑kinase (PI3K) inhibitor, suppressed the ability of BDNF to 
      inhibit the effects of high glucose. In addition, BDNF significantly upregulated 
      the tropomyosin‑related kinase B, its cognate receptor, Akt and phosphorylated 
      Akt at the protein levels under high glucose conditions. In conclusion, high 
      glucose induced apoptosis and downregulated synaptic plasticity‑related proteins 
      in hippocampal neurons. These effects were reversed by BDNF via the PI3K/Akt 
      signaling pathway.
FAU - Zhong, Yuan
AU  - Zhong Y
AD  - Department of Gerontology, Shanghai Jiao Tong University Affiliated Sixth 
      People's Hospital, Shanghai 200233, P.R. China.
FAU - Zhu, Yitong
AU  - Zhu Y
AD  - Department of Gerontology, Shanghai Jiao Tong University Affiliated Sixth 
      People's Hospital, Shanghai 200233, P.R. China.
FAU - He, Ting
AU  - He T
AD  - Department of Gerontology, Shanghai Jiao Tong University Affiliated Sixth 
      People's Hospital, Shanghai 200233, P.R. China.
FAU - Li, Wei
AU  - Li W
AD  - Department of Gerontology, Shanghai Jiao Tong University Affiliated Sixth 
      People's Hospital, Shanghai 200233, P.R. China.
FAU - Li, Qinjie
AU  - Li Q
AD  - Department of Gerontology, Shanghai Jiao Tong University Affiliated Sixth 
      People's Hospital, Shanghai 200233, P.R. China.
FAU - Miao, Ya
AU  - Miao Y
AD  - Department of Gerontology, Shanghai Jiao Tong University Affiliated Sixth 
      People's Hospital, Shanghai 200233, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20181015
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Cells, Cultured
MH  - Down-Regulation/*drug effects
MH  - Glucose/toxicity
MH  - Hippocampus/*metabolism
MH  - Hyperglycemia/*pathology
MH  - Nerve Tissue Proteins/genetics/metabolism
MH  - Neuronal Plasticity/*drug effects
MH  - Neurons/drug effects/*metabolism
MH  - Phosphatidylinositol 3-Kinase/metabolism
MH  - Phosphorylation/drug effects
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/*drug effects
MH  - Up-Regulation/drug effects
PMC - PMC6257855
EDAT- 2018/10/27 06:00
MHDA- 2019/03/06 06:00
PMCR- 2018/10/15
CRDT- 2018/10/27 06:00
PHST- 2018/04/29 00:00 [received]
PHST- 2018/10/04 00:00 [accepted]
PHST- 2018/10/27 06:00 [pubmed]
PHST- 2019/03/06 06:00 [medline]
PHST- 2018/10/27 06:00 [entrez]
PHST- 2018/10/15 00:00 [pmc-release]
AID - ijmm-43-01-0294 [pii]
AID - 10.3892/ijmm.2018.3933 [doi]
PST - ppublish
SO  - Int J Mol Med. 2019 Jan;43(1):294-304. doi: 10.3892/ijmm.2018.3933. Epub 2018 Oct 
      15.