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Isoflurane exposure regulates the cell viability and BDNF expression of astrocytes via upregulation of TREK‑1.
- Source :
-
Molecular medicine reports [Mol Med Rep] 2017 Nov; Vol. 16 (5), pp. 7305-7314. Date of Electronic Publication: 2017 Sep 20. - Publication Year :
- 2017
-
Abstract
- 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.
- Subjects :
- Animals
Astrocytes cytology
Astrocytes drug effects
Astrocytes metabolism
Brain-Derived Neurotrophic Factor genetics
Caspase 3 genetics
Caspase 3 metabolism
Cell Survival drug effects
Cells, Cultured
Female
Male
Mice
Mice, Inbred C57BL
Potassium Channels, Tandem Pore Domain antagonists & inhibitors
Potassium Channels, Tandem Pore Domain genetics
RNA Interference
RNA, Messenger metabolism
RNA, Small Interfering metabolism
bcl-2-Associated X Protein genetics
bcl-2-Associated X Protein metabolism
Brain-Derived Neurotrophic Factor metabolism
Isoflurane pharmacology
Potassium Channels, Tandem Pore Domain metabolism
Up-Regulation drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1791-3004
- Volume :
- 16
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Molecular medicine reports
- Publication Type :
- Academic Journal
- Accession number :
- 28944872
- Full Text :
- https://doi.org/10.3892/mmr.2017.7547