title: Isoflurane Is More Deleterious to Developing Brain Than Desflurane: The Role of the Akt/GSK3β Signaling Pathway.
abstract: Demand is increasing for safer inhalational anesthetics for use in pediatric anesthesia. In this regard, researchers have debated whether isoflurane is more toxic to the developing brain than desflurane. In the present study, we compared the effects of postnatal exposure to isoflurane with those of desflurane on long-term cognitive performance and investigated the role of the Akt/GSK3β signaling pathway. Postnatal day 6 (P6) mice were exposed to either isoflurane or desflurane, after which the phosphorylation levels of Akt/GSK3β and learning and memory were assessed at P8 or P31. The phosphorylation levels of Akt/GSK3β and learning and memory were examined after intervention with lithium. We found that isoflurane, but not desflurane, impaired spatial learning and memory at P31. Accompanied by behavioral change, only isoflurane decreased p-Akt (ser473) and p-GSK3β (ser9) expressions, which led to GSK3β overactivation. Lithium prevented GSK3β overactivation and alleviated isoflurane-induced cognitive deficits. These results suggest that isoflurane is more likely to induce developmental neurotoxicity than desflurane in context of multiple exposures and that the Akt/GSK3β signaling pathway partly participates in this process. GSK3β inhibition might be an effective way to protect against developmental neurotoxicity.
authors.affiliation: Department of Anesthesiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin Er Road, Shanghai 200025, China.
authors.forename: Guorong
authors.initials: G
authors.lastname: Tao
authors.affiliation: Department of Anesthesiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin Er Road, Shanghai 200025, China.
authors.forename: Qingsheng
authors.initials: Q
authors.lastname: Xue
authors.affiliation: Department of Anesthesiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin Er Road, Shanghai 200025, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Anesthesiology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Guohui
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin Er Road, Shanghai 200025, China.
authors.forename: Yimeng
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Department of Anesthesiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin Er Road, Shanghai 200025, China.
authors.forename: Buwei
authors.initials: B
authors.lastname: Yu
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000254:growth & development; D000077335:Desflurane; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism*; D007530:Isoflurane / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008094:Lithium / Q000494:pharmacology; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D008094:Lithium; D000077335:Desflurane; D007530:Isoflurane; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt