title: Learning, memory and synaptic plasticity in hippocampus in rats exposed to sevoflurane.
abstract: OBJECTIVE
  Developmental exposure to volatile anesthetics has been associated with cognitive deficits at adulthood. Rodent studies have revealed impairments in performance in learning tasks involving the hippocampus. However, how the duration of anesthesia exposure impact on hippocampal synaptic plasticity, learning, and memory is as yet not fully elucidated.
  
  
  METHODS
  On postnatal day 7(P7), rat pups were divided into 3 groups: control group (n=30), 3% sevoflurane treatment for 1h (Sev 1h group, n=30) and 3% sevoflurane treatment for 6h (Sev 6h group, n=28). Following anesthesia, synaptic vesicle-associated proteins and dendrite spine density and synapse ultrastructure were measured using western blotting, Golgi staining, and transmission electron microscopy (TEM) on P21. In addition, the effects of sevoflurane treatment on long-term potentiation (LTP) and long-term depression (LTD), two molecular correlates of memory, were studied in CA1 subfields of the hippocampus, using electrophysiological recordings of field potentials in hippocampal slices on P35-42. Rats' neurocognitive performance was assessed at 2 months of age, using the Morris water maze and novel-object recognition tasks.
  
  
  RESULTS
  Our results showed that neonatal exposure to 3% sevoflurane for 6h results in reduced spine density of apical dendrites along with elevated expression of synaptic vesicle-associated proteins (SNAP-25 and syntaxin), and synaptic ultrastructure damage in the hippocampus. The electrophysiological evidence indicated that hippocampal LTP, but not LTD, was inhibited and that learning and memory performance were impaired in two behavioral tasks in the Sev 6h group. In contrast, lesser structural and functional damage in the hippocampus was observed in the Sev 1h group.
  
  
  CONCLUSIONS
  Our data showed that 6-h exposure of the developing brain to 3% sevoflurane could result in synaptic plasticity impairment in the hippocampus and spatial and nonspatial hippocampal-dependent learning and memory deficits. In contrast, shorter-duration exposure (1h) results in less damage. These results provide further evidences that duration of anesthesia exposure could have differential effects on neuronal plasticity and neurocognitive performance.
authors.affiliation: Department of Anesthesiology, Huashan Hospital, Fudan University, Shanghai, China. Electronic address: xiaohongyanmd@163.com.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Department of Anesthesiology, Huashan Hospital, Fudan University, Shanghai, China. Electronic address: lbzaixuzhou@126.com.
authors.forename: Bing
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Huashan Hospital, Fudan University, Shanghai, China. Electronic address: chenyali650@163.com.
authors.forename: Yali
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, Huashan Hospital, Fudan University, Shanghai, China. Electronic address: snapzhang@aliyun.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000367:Age Factors; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D049229:Dendritic Spines / Q000187:drug effects / Q000648:ultrastructure; D005106:Exploratory Behavior / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000254:growth & development / Q000648:ultrastructure; D007858:Learning / Q000187:drug effects*; D017774:Long-Term Potentiation / Q000187:drug effects; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D008738:Methyl Ethers / Q000494:pharmacology*; D009473:Neuronal Plasticity / Q000187:drug effects*; D050765:Qa-SNARE Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane; D013037:Spatial Behavior / Q000187:drug effects; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism; D013997:Time Factors
chemical_list: D000700:Analgesics; D008738:Methyl Ethers; D050765:Qa-SNARE Proteins; D050825:Synaptosomal-Associated Protein 25; D000077149:Sevoflurane
keywords: Developing brain; Learning; Memory; Neurotoxicity; Sevoflurane anesthesia; Synaptic plasticity