title: Sevoflurane inhibits neurogenesis and the Wnt-catenin signaling pathway in mouse neural progenitor cells.
abstract: Recent population studies suggest that children who receive anesthesia and surgery could be at an increased risk for developing learning disabilities. The underlying reason for this clinical observation is largely unknown. Whether undergoing anesthesia contributes to learning disability development, or if the need for anesthesia and surgery is a marker for other unidentified factors that contribute to the development of learning disabilities, remains to be determined. Neurogenesis, regulated by the Wnt-catenin signaling pathway, has been shown to be involved in learning and memory, and sevoflurane is the most commonly used inhalation anesthetic in children. We therefore set out to determine the effects of sevoflurane on neurogenesis and the Wnt-catenin signaling pathway in mouse neural progenitor cells (NPCs) using immunofluorescence and Western blot analysis. Here we show for the first time that 4.1%, but not 2.0%, sevoflurane reduced mouse NPC proliferation, increased Glycogen synthase kinase-3β(GSK-3β) levels, and decreased levels of β-Catenin in mouse NPCs. The GSK-3β inhibitor Lithium attenuated the sevoflurane-induced reduction in mouse NPC proliferation. The data suggest that sevoflurane may reduce neurogenesis through the Wnt-catenin signaling pathway. These findings would promote further studies to investigate the effects of anesthesia on neurogenesis and function of learning and memory, as well as the underlying mechanisms in vitro and in vivo. Ultimately these efforts would lead to safer anesthesia care and better postoperative outcomes in children.
authors: Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, 149 13th St., Room 4310, Charlestown, MA 02129-2060, USA. zxie@partners.org.
authors: Y
authors: Y
authors: Zhang
authors: Y
authors: Y
authors: Dong
authors: H
authors: H
authors: Zheng
authors: V
authors: V
authors: Shie
authors: H
authors: H
authors: Wang
authors: J J
authors: JJ
authors: Busscher
authors: Y
authors: Y
authors: Yue
authors: Z
authors: Z
authors: Xu
authors: Z
authors: Z
authors: Xie
mesh_terms: D018685:Anesthetics, Inhalation / Q000009:adverse effects* / Q000494:pharmacology; D000818:Animals; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000096:biosynthesis; D000071679:Glycogen Synthase Kinase 3 beta; D008738:Methyl Ethers / Q000009:adverse effects* / Q000494:pharmacology; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D058953:Neural Stem Cells / Q000378:metabolism* / Q000473:pathology; D055495:Neurogenesis / Q000187:drug effects*; D000077149:Sevoflurane; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D009419:Nerve Tissue Proteins; D051153:Wnt Proteins; D051176:beta Catenin; D000077149:Sevoflurane; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3