title: Sevoflurane induces cognitive impairments via the MiR-27b/LIMK1-signaling pathway in developing rats.
abstract: Exposure to sevoflurane in neonatal rats could induce learning deficits and abnormal social behaviors, but the specific molecular mechanism is unknown. Postnatal day-7 SD rats were treated with 3% sevoflurane plus 30% oxygen/air or 30% oxygen/air. As the rats grew, the Morris water maze (MWM) and fear conditioning tests were performed to evaluate cognitive function, while the expression of LIMK1 was analyzed by western blot. Luciferase reporter assay was performed to investigate the interaction between LIMK1 and miR-27b. The expression of miR-27b was measured by real-time polymerase chain reaction (PCR) after exposure to sevoflurane. Once the miR-27b inhibitor was transfected into the neurons, the expression of LIMK1 was analyzed by real-time PCR and western blot. Exposure to sevoflurane in neonatal rats induced memory and learning impairments according to the MWM and fear conditioning tests. Sevoflurane increased the expression of miR-27b and reduced the expression of LIMK1 in the brain tissues of rats compared to the control group. The results of the luciferase reporter assay showed that LIMK1 was a direct target of miR-27b. In the primary neurons, the inhibition of miR-27b could reverse the down-regulating effects of sevoflurane on LIMK1 expression. We suggest that sevoflurane-induced learning and memory impairments in rats might be mediated via the miR-27b-LIMK1-signaling pathway.
authors.affiliation: a Department of Anaesthesiology , Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai , China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yu
authors.affiliation: a Department of Anaesthesiology , Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai , China.
authors.forename: Peihong
authors.initials: P
authors.lastname: Zhang
authors.affiliation: a Department of Anaesthesiology , Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai , China.
authors.forename: Jia
authors.initials: J
authors.lastname: Yan
authors.affiliation: a Department of Anaesthesiology , Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai , China.
authors.forename: Yuanqing
authors.initials: Y
authors.lastname: Sun
authors.affiliation: a Department of Anaesthesiology , Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai , China.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Wu
authors.affiliation: a Department of Anaesthesiology , Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai , China.
authors.forename: Siwei
authors.initials: S
authors.lastname: Xi
authors.affiliation: a Department of Anaesthesiology , Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai , China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: a Department of Anaesthesiology , Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai , China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.affiliation: a Department of Anaesthesiology , Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai , China.
authors.forename: Rong
authors.initials: R
authors.lastname: Hu
authors.affiliation: a Department of Anaesthesiology , Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai , China.
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
mesh_terms: D018685:Anesthetics, Inhalation / Q000633:toxicity*; D000818:Animals; D001522:Behavior, Animal; D002478:Cells, Cultured; D060825:Cognitive Dysfunction / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D005239:Fear; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D054461:Lim Kinases / Q000235:genetics* / Q000378:metabolism; D008297:Male; D018782:Maze Learning; D008738:Methyl Ethers / Q000633:toxicity*; D035683:MicroRNAs / Q000235:genetics*; D011247:Pregnancy; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane; D015398:Signal Transduction
chemical_list: D018685:Anesthetics, Inhalation; C000594049:MIRN27 microRNA, rat; D008738:Methyl Ethers; D035683:MicroRNAs; D000077149:Sevoflurane; D054461:Lim Kinases; C515894:Limk1 protein, rat
keywords: LIMK1; Learning and memory impairments; miR-27b; neonatal rats; sevoflurane