Sevoflurane anesthesia represses neurogenesis of hippocampus neural stem cells via regulating microRNA-183-mediated NR4A2 in newborn rats.
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.
['Shao|Chang-Zhong|CZ|', 'Xia|Kun-Peng|KP|0000-0003-1573-4405']
D018685:Anesthetics, Inhalation D000818:Animals D000831:Animals, Newborn D019208:Brain-Derived Neurotrophic Factor D049109:Cell Proliferation D002478:Cells, Cultured D005260:Female D018507:Gene Expression Regulation, Developmental D006624:Hippocampus D008297:Male D035683:MicroRNAs D058953:Neural Stem Cells D055495:Neurogenesis D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 D051381:Rats D055748:SOXB1 Transcription Factors D000077149:Sevoflurane D015398:Signal Transduction D015854:Up-Regulation
sevoflurane NR4A2 microRNA-183 hippocampal neural stem cells proliferation differentiation