PMID- 28944872
OWN - NLM
STAT- MEDLINE
DCOM- 20180606
LR  - 20181113
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Print)
IS  - 1791-2997 (Linking)
VI  - 16
IP  - 5
DP  - 2017 Nov
TI  - Isoflurane exposure regulates the cell viability and BDNF expression of 
      astrocytes via upregulation of TREK‑1.
PG  - 7305-7314
LID - 10.3892/mmr.2017.7547 [doi]
AB  - Neonatal isoflurane exposure in rodents disrupts hippocampal cognitive functions, 
      including learning and memory, and astrocytes may have an important role in this 
      process. However, the molecular mechanisms underlying this disruption are not 
      fully understood. The present study investigated the role of TWIK‑related K+ 
      channel (TREK‑1) in isoflurane‑induced cognitive impairment. Lentiviruses were 
      used to overexpress or knockdown TREK‑1 in astrocytes exposed to increasing 
      concentrations of isoflurane or O2 for 2 h. Subsequently, the mRNA and protein 
      expression of brain‑derived neurotrophic factor (BDNF), caspase‑3, 
      Bcl‑2‑associated X (Bax) and TREK‑1 was measured by reverse transcription‑ 
      quantitative polymerase chain reaction and western blot analysis, respectively. 
      In addition, cell viability was assessed by a 
      2‑(4‑Iodophenyl)‑3‑(4‑nitrophenyl)‑5‑(2,4‑disulfophenyl)‑ 2H‑tetrazolium 
      monosodium salt assay. The results demonstrated that, prior to manipulating 
      TREK‑1, isoflurane significantly decreased the cell viability and BDNF 
      expression, and increased Bax, caspase‑3 and TREK‑1 expression was observed. 
      However, TREK‑1 overexpression in astrocytes significantly downregulated BDNF 
      expression, and upregulated Bax and caspase‑3 expression. Furthermore, 
      lentiviral‑mediated short hairpin RNA knockdown of TREK‑1 effectively inhibited 
      the isoflurane‑induced changes in BDNF, Bax and caspase‑3 expression. Taken 
      together, the results of the present study indicate that isoflurane‑induced cell 
      damage in astrocytes may be associated with TREK‑1‑mediated inhibition of BDNF 
      and provide a reference for the safe use of isoflurane anesthesia in infants and 
      children.
FAU - Zhou, Cui-Hong
AU  - Zhou CH
AD  - Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, 
      Xi'an, Shaanxi 710032, P.R. China.
FAU - Zhang, Ya-Hong
AU  - Zhang YH
AD  - Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, 
      Xi'an, Shaanxi 710032, P.R. China.
FAU - Xue, Fen
AU  - Xue F
AD  - Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, 
      Xi'an, Shaanxi 710032, P.R. China.
FAU - Xue, Shan-Shan
AU  - Xue SS
AD  - Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, 
      Xi'an, Shaanxi 710032, P.R. China.
FAU - Chen, Yun-Chun
AU  - Chen YC
AD  - Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, 
      Xi'an, Shaanxi 710032, P.R. China.
FAU - Gu, Ting
AU  - Gu T
AD  - Department of Anesthesiology, Xijing Hospital, Fourth Military Medical 
      University, Xi'an, Shaanxi 710032, P.R. China.
FAU - Peng, Zheng-Wu
AU  - Peng ZW
AD  - Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, 
      Xi'an, Shaanxi 710032, P.R. China.
FAU - Wang, Hua-Ning
AU  - Wang HN
AD  - Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, 
      Xi'an, Shaanxi 710032, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20170920
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Potassium Channels, Tandem Pore Domain)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 0 (potassium channel protein TREK-1)
RN  - CYS9AKD70P (Isoflurane)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Animals
MH  - Astrocytes/cytology/drug effects/metabolism
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Caspase 3/genetics/metabolism
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Female
MH  - Isoflurane/*pharmacology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Potassium Channels, Tandem Pore Domain/antagonists & 
      inhibitors/genetics/*metabolism
MH  - RNA Interference
MH  - RNA, Messenger/metabolism
MH  - RNA, Small Interfering/metabolism
MH  - Up-Regulation/*drug effects
MH  - bcl-2-Associated X Protein/genetics/metabolism
PMC - PMC5865860
EDAT- 2017/09/26 06:00
MHDA- 2018/06/07 06:00
PMCR- 2017/09/20
CRDT- 2017/09/26 06:00
PHST- 2017/01/11 00:00 [received]
PHST- 2017/07/26 00:00 [accepted]
PHST- 2017/09/26 06:00 [pubmed]
PHST- 2018/06/07 06:00 [medline]
PHST- 2017/09/26 06:00 [entrez]
PHST- 2017/09/20 00:00 [pmc-release]
AID - mmr-16-05-7305 [pii]
AID - 10.3892/mmr.2017.7547 [doi]
PST - ppublish
SO  - Mol Med Rep. 2017 Nov;16(5):7305-7314. doi: 10.3892/mmr.2017.7547. Epub 2017 Sep 
      20.