PMID- 28777258
OWN - NLM
STAT- MEDLINE
DCOM- 20180502
LR  - 20211020
IS  - 1473-558X (Electronic)
IS  - 0959-4965 (Linking)
VI  - 28
IP  - 14
DP  - 2017 Sep 27
TI  - Knockdown of long noncoding antisense RNA brain-derived neurotrophic factor 
      attenuates hypoxia/reoxygenation-induced nerve cell apoptosis through the 
      BDNF-TrkB-PI3K/Akt signaling pathway.
PG  - 910-916
LID - 10.1097/WNR.0000000000000860 [doi]
AB  - Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal cell 
      apoptosis. The antisense RNA of brain-derived neurotrophic factor (BDNF-AS) is a 
      natural antisense transcript that is transcribed opposite the gene that encodes 
      BDNF. The aim of this study was to determine whether knockdown of BDNF-AS can 
      suppress hypoxia/reoxygenation (H/R)-induced neuronal cell apoptosis and whether 
      this is mediated by the BDNF-TrkB-PI3K/Akt pathway. We detected the expression of 
      BDNF and BDNF-AS in brain tissue from 20 patients with cerebral infarction and 
      five patients with other diseases (but no cerebral ischemia). We found that BDNF 
      expression was significantly downregulated in patients with cerebral infarction, 
      whereas the expression of BDNF-AS was significantly upregulated. In both human 
      cortical neurons (HCN2) and human astrocytes, H/R significantly induced the 
      expression of BDNF-AS, but significantly decreased BDNF expression. H/R also 
      significantly induced apoptosis and reduced the mitochondrial membrane potential 
      in these cells. Following downregulation of BDNF-AS by siRNA in human cortical 
      neurons and human astrocyte cells, BDNF expression was significantly upregulated 
      and the H/R-induced upregulation of BDNF-AS was significantly attenuated. BDNF-AS 
      siRNA inhibited H/R-induced cell apoptosis and ameliorated the H/R-induced 
      suppression of mitochondrial membrane potential. H/R inhibited the expression of 
      BDNF, p-AKT/AKT, and TrKB, and this inhibition was recovered by BDNF-AS siRNA. In 
      summary, this study indicates that BDNF-AS siRNA induces activation of the 
      BDNF-TrkB-PI3K/Akt pathway following H/R-induced neurotoxicity. These findings 
      will be useful toward the application of BDNF-AS siRNA for the treatment of 
      neurodegenerative diseases.
FAU - Zhong, Jian-Bin
AU  - Zhong JB
AD  - Department of Neurology, Guangzhuo Zengcheng People's Hospital and Boji Hospital 
      of Sun Yat-Sen University, Guangzhou, People's Republic of China.
FAU - Li, Xie
AU  - Li X
FAU - Zhong, Si-Ming
AU  - Zhong SM
FAU - Liu, Jiu-Di
AU  - Liu JD
FAU - Chen, Chi-Bang
AU  - Chen CB
FAU - Wu, Xiao-Yan
AU  - Wu XY
LA  - eng
PT  - Journal Article
PL  - England
TA  - Neuroreport
JT  - Neuroreport
JID - 9100935
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (RNA, Small Interfering)
RN  - 7171WSG8A2 (BDNF protein, human)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.10.1 (tropomyosin-related kinase-B, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Apoptosis/*physiology
MH  - Astrocytes/metabolism/pathology
MH  - Brain/*metabolism/pathology
MH  - Brain Ischemia/*metabolism/pathology/therapy
MH  - Brain-Derived Neurotrophic Factor/antagonists & inhibitors/genetics/*metabolism
MH  - Cells, Cultured
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - Membrane Glycoproteins/metabolism
MH  - Membrane Potential, Mitochondrial/physiology
MH  - Neurons/metabolism/pathology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - RNA, Long Noncoding/antagonists & inhibitors/genetics/*metabolism
MH  - RNA, Small Interfering
MH  - Receptor, trkB/metabolism
MH  - Reperfusion Injury/*metabolism/pathology/therapy
MH  - Signal Transduction
EDAT- 2017/08/05 06:00
MHDA- 2018/05/03 06:00
CRDT- 2017/08/05 06:00
PHST- 2017/08/05 06:00 [pubmed]
PHST- 2018/05/03 06:00 [medline]
PHST- 2017/08/05 06:00 [entrez]
AID - 10.1097/WNR.0000000000000860 [doi]
PST - ppublish
SO  - Neuroreport. 2017 Sep 27;28(14):910-916. doi: 10.1097/WNR.0000000000000860.