title: Environmental Enrichment Ameliorates Neonatal Sevoflurane Exposure-Induced Cognitive and Synaptic Plasticity Impairments.
abstract: Early exposure to sevoflurane, an inhalation anesthetic, induces neurodegeneration in the developing brain and subsequent long-term neurobehavioral abnormalities. Here, we investigated whether an enriched environment could mitigate neonatal sevoflurane exposure-induced long-term cognitive and synaptic plasticity impairments. Male C57BL/6 mice were exposed to 3 % sevoflurane 2 h daily for 3 days from postnatal day 6 (P6) to P8. The exposed mice were randomly allocated to an enriched environment for 2 h daily between P8 and P42 or to a standard environment. Their behavior and cognition were assessed using open field (P35) and fear conditioning tests (P41-P42). Hematoxylin-eosin staining was used to study morphological changes in pyramidal neurons of hippocampal CA1 and CA3 regions. Synaptic plasticity alternations were assessed using western blotting, Golgi staining, and electrophysiological recording. We found that sevoflurane-exposed mice housed in a standard environment exhibited a reduced freezing response in the contextual test, decreased number of dendritic spines on pyramidal neurons and synaptic plasticity-related proteins in the hippocampus, and impaired long-term potentiation. However, in an enriched environment, some of these abnormities induced by repeated sevoflurane exposure. In conclusion, neonatal sevoflurane exposure-induced cognitive and synaptic plasticity impairments are ameliorated by an enriched environment.
authors.affiliation: Department of Anesthesiology, Jinling Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Mu-huo
authors.initials: MH
authors.lastname: Ji
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, China.
authors.forename: Xing-ming
authors.initials: XM
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, China.
authors.forename: Xiao-ru
authors.initials: XR
authors.lastname: Sun
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, China.
authors.forename: Ling-sha
authors.initials: LS
authors.lastname: Ju
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, China.
authors.forename: Li-li
authors.initials: LL
authors.lastname: Qiu
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, China.
authors.forename: Jiao-jiao
authors.initials: JJ
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, China.
authors.forename: Min
authors.initials: M
authors.lastname: Jia
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, China. yjyangjj@126.com.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Yang
mesh_terms: D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D003072:Cognition Disorders / Q000139:chemically induced* / Q000517:prevention & control; D003214:Conditioning, Classical / Q000187:drug effects*; D049229:Dendritic Spines / Q000187:drug effects / Q000648:ultrastructure; D004597:Electroshock; D004777:Environment; D005106:Exploratory Behavior / Q000187:drug effects*; D005239:Fear / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects* / Q000254:growth & development / Q000648:ultrastructure; D006799:Housing, Animal; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D008738:Methyl Ethers / Q000008:administration & dosage / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D010988:Play and Playthings; D017966:Pyramidal Cells / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D011897:Random Allocation; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D000077149:Sevoflurane
keywords: Long-term potentiation; Memory; Neonate; Sevoflurane; Synaptic plasticity