title: Underlying Mechanisms of Memory Deficits Induced by Etomidate Anesthesia in Aged Rat Model: Critical Role of Immediate Early Genes.
abstract: BACKGROUND
  Etomidate (R-1-[1-ethylphenyl] imidazole-5-ethyl ester) is a widely used anesthetic drug that had been reported to contribute to cognitive deficits after general surgery. However, its underlying mechanisms have not been fully elucidated. In this study, we aimed to explore the neurobiological mechanisms of cognitive impairments that caused by etomidate.
  
  
  METHODS
  A total of 30 Sprague-Dawley rats were used and divided into two groups randomly to receive a single injection of etomidate or vehicle. Then, the rats' spatial memory ability and neuronal survival were evaluated using the Morris water maze test and Nissl staining, respectively. Furthermore, we analyzed levels of oxidative stress, as well as cyclic adenosine 3',5'-monophosphate response element-binding (CREB) protein phosphorylation and immediate early gene (IEG, including Arc, c-fos, and Egr1) expression levels using Western blot analysis.
  
  
  RESULTS
  Compared with vehicle-treated rats, the etomidate-treated rats displayed impaired spatial learning (day 4: 27.26 ± 5.33 s vs. 35.52 ± 3.88 s, t = 2.988, P = 0.0068; day 5: 15.84 ± 4.02 s vs. 30.67 ± 4.23 s, t = 3.013, P = 0.0057; day 6: 9.47 ± 2.35 s vs. 25.66 ± 4.16 s, t = 3.567, P = 0.0036) and memory ability (crossing times: 4.40 ± 1.18 vs. 2.06 ± 0.80, t = 2.896, P = 0.0072; duration: 34.00 ± 4.24 s vs. 18.07 ± 4.79 s, t = 3.023, P = 0.0053; total swimming distance: 40.73 ± 3.45 cm vs. 27.40 ± 6.56 cm, t = 2.798, P = 0.0086) but no neuronal death. Furthermore, etomidate did not cause oxidative stress or deficits in CREB phosphorylation. The levels of multiple IEGs (Arc: vehicle treated rats 100%, etomidate treated rats 86%, t = 2.876, P = 0.0086; c-fos: Vehicle treated rats 100%, etomidate treated rats 72%, t = 2.996, P = 0.0076; Egr1: Vehicle treated rats 100%, etomidate treated rats 58%, t = 3.011, P = 0.0057) were significantly reduced in hippocampi of etomidate-treated rats.
  
  
  CONCLUSIONS
  Our data suggested that etomidate might induce memory impairment in rats via inhibition of IEG expression.
authors.affiliation: Department of Pathology, Affiliated Cancer Hospital of Zhengzhou University, Henan Provincial Cancer Hospital, Zhengzhou, Henan 450008, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Li
authors.forename: Fen
authors.initials: F
authors.lastname: Lu
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Sun
authors.forename: Ling-Zhi
authors.initials: LZ
authors.lastname: Qin
authors.forename: Qian-Lin
authors.initials: QL
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Yao
authors.forename: Qing-Kai
authors.initials: QK
authors.lastname: Yu
authors.forename: Xin-Liang
authors.initials: XL
authors.lastname: Liang
mesh_terms: D000758:Anesthesia / Q000009:adverse effects; D000818:Animals; D005045:Etomidate / Q000009:adverse effects*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006993:Hypnotics and Sedatives / Q000009:adverse effects*; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D006993:Hypnotics and Sedatives; D017874:Immediate-Early Proteins; D005045:Etomidate