PMID- 30191980 OWN - NLM STAT- MEDLINE DCOM- 20200316 LR - 20220410 IS - 1097-4652 (Electronic) IS - 0021-9541 (Linking) VI - 234 IP - 4 DP - 2019 Apr TI - Sevoflurane anesthesia represses neurogenesis of hippocampus neural stem cells via regulating microRNA-183-mediated NR4A2 in newborn rats. PG - 3864-3873 LID - 10.1002/jcp.27158 [doi] AB - Sevoflurane has been commonly utilized in nonobstetric surgeries in pregnant women, and its impacts on fetal brain are still not completely known. Ectopic NR4A2 expression has been reported to be related with familial Parkinson disease, and through dual luciferase we found that NR4A2 is a target gene of microRNA-183 (miR-183). We proposed a hypothesis that miR-183 may participate in the process by targeting NR4A2 in neurons after sevoflurane anesthesia. To verify the effect of sevoflurane on hippocampal neural stem cells (NSCs) proliferation and differentiation, we conducted EdU assay and immunofluorescence staining. Next, for better understanding of the impact of miR-183, we altered the miR-183 expression using mimic and inhibitor. Meanwhile, the targeting relationship between miR-183 and NR4A2 was validated by a bioinformatics website and dual-luciferase reporter gene assay. Finally, expressions of miR-184, NR4A2, SRY (sex-determining region Y)-box 2 (Sox2), and brain-derived neurotrophic factor (BDNF) were determined and evaluated by reverse transcription quantitative polymerase chain reaction and western blot analysis. First, sevoflurane was determined a crucial factor in biological behaviors of hippocampal NSCs. Moreover, upregulated miR-183 expression by mimic inhibited the proliferation and differentiation of NSCs. Sevoflurane negatively regulated NR4A2 and Sox2 expressions but positively regulated miR-183 and BDNF expressions. Our findings revealed the underlying novel mechanism by which sevoflurane inhibits hippocampal NSC proliferation and differentiation through interaction with miR-183 and NR4A2. The study provides reliable reference for safe application of sevoflurane anesthesia in neonates. CI - (c) 2018 Wiley Periodicals, Inc. FAU - Shao, Chang-Zhong AU - Shao CZ AD - Department of Anesthesiology, Linyi People's Hospital Affiliated to Shandong University, Linyi, China. FAU - Xia, Kun-Peng AU - Xia KP AUID- ORCID: 0000-0003-1573-4405 AD - Department of Anesthesiology, Linyi People's Hospital Affiliated to Shandong University, Linyi, China. LA - eng PT - Journal Article DEP - 20180907 PL - United States TA - J Cell Physiol JT - Journal of cellular physiology JID - 0050222 RN - 0 (Anesthetics, Inhalation) RN - 0 (Bdnf protein, rat) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (MIRN183 microRNA, rat) RN - 0 (MicroRNAs) RN - 0 (Nr4a2 protein, rat) RN - 0 (Nuclear Receptor Subfamily 4, Group A, Member 2) RN - 0 (SOXB1 Transcription Factors) RN - 0 (Sox2 protein, rat) RN - 38LVP0K73A (Sevoflurane) SB - IM MH - Anesthetics, Inhalation/*toxicity MH - Animals MH - Animals, Newborn MH - Brain-Derived Neurotrophic Factor/genetics/metabolism MH - Cell Proliferation/drug effects MH - Cells, Cultured MH - Female MH - Gene Expression Regulation, Developmental MH - Hippocampus/*drug effects/metabolism/pathology MH - Male MH - MicroRNAs/genetics/*metabolism MH - Neural Stem Cells/*drug effects/metabolism/pathology MH - Neurogenesis/*drug effects MH - Nuclear Receptor Subfamily 4, Group A, Member 2/genetics/*metabolism MH - Rats MH - SOXB1 Transcription Factors/genetics/metabolism MH - Sevoflurane/*toxicity MH - Signal Transduction MH - Up-Regulation OTO - NOTNLM OT - NR4A2 OT - differentiation OT - hippocampal neural stem cells OT - microRNA-183 OT - proliferation OT - sevoflurane EDAT- 2018/09/08 06:00 MHDA- 2020/03/17 06:00 CRDT- 2018/09/08 06:00 PHST- 2018/03/31 00:00 [received] PHST- 2018/07/10 00:00 [accepted] PHST- 2018/09/08 06:00 [pubmed] PHST- 2020/03/17 06:00 [medline] PHST- 2018/09/08 06:00 [entrez] AID - 10.1002/jcp.27158 [doi] PST - ppublish SO - J Cell Physiol. 2019 Apr;234(4):3864-3873. doi: 10.1002/jcp.27158. Epub 2018 Sep 7.