title: Tau phosphorylation and sevoflurane anesthesia: an association to postoperative cognitive impairment.
abstract: BACKGROUND
  There is a growing interest in the involvement of anesthetic agents in the etiology of postoperative cognitive dysfunction. Recent animal studies suggest that acute anesthesia induces transient hyperphosphorylation of tau, an effect essentially ascribed to hypothermia. The main aim of the present study was to investigate effects, in normothermic conditions, of acute or repeated exposure to sevoflurane, a halogenated anesthetic agent, on hippocampal tau phosphorylation and spatial memory in adult mice.
  
  
  METHODS
  5 to 6-month-old C57Bl6/J mice were submitted to acute (1 h) or repeated (five exposures of 1h every month) anesthesia using 1.5 or 2.5% sevoflurane, in normothermic conditions. In the acute protocol, animals were sacrificed 1 and 24 h after exposure. In the chronic protocol, spatial memory was evaluated using the Morris water maze following the fourth exposure, and tau phosphorylation evaluated 1 month following the last exposure using bi- and mono-dimensional electrophoresis.
  
  
  RESULTS
  Acute sevoflurane anesthesia in normothermic conditions led to a significant dose-dependent and reversible hippocampal tau phosphorylation, 1 h following the end of exposure (P < 0.001). Conversely, repeated anesthesia led to persistent tau hyperphosphorylation and significant memory impairments, as seen in the retention phase of the Morris water maze in sevoflurane-anesthesized animals. These pathologic features may be related to the activation of both Akt and Erk pathways.
  
  
  CONCLUSIONS
  The present study demonstrates, in mice, that sevoflurane exposure is associated with increased tau phosphorylation through specific kinases activation and spatial memory deficits. These data support a correlation between exposures to this anesthetic agent and cognitive decline.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, UMR837, Alzheimer & Tauopathies, Institut de Médecine Prédictive et de Recherche Thérapeutique, Lille, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Le Freche
authors.forename: Jonathan
authors.initials: J
authors.lastname: Brouillette
authors.forename: Francisco-José
authors.initials: FJ
authors.lastname: Fernandez-Gomez
authors.forename: Pauline
authors.initials: P
authors.lastname: Patin
authors.forename: Raphaëlle
authors.initials: R
authors.lastname: Caillierez
authors.forename: Nadège
authors.initials: N
authors.lastname: Zommer
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sergeant
authors.forename: Valérie
authors.initials: V
authors.lastname: Buée-Scherrer
authors.forename: Gilles
authors.initials: G
authors.lastname: Lebuffe
authors.forename: David
authors.initials: D
authors.lastname: Blum
authors.forename: Luc
authors.initials: L
authors.lastname: Buée
mesh_terms: D000208:Acute Disease; D000768:Anesthesia, General / Q000009:adverse effects*; D000818:Animals; D002908:Chronic Disease; D003072:Cognition Disorders / Q000139:chemically induced* / Q000378:metabolism*; D005260:Female; D008738:Methyl Ethers / Q000009:adverse effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation / Q000502:physiology; D011183:Postoperative Complications / Q000139:chemically induced / Q000378:metabolism; D000077149:Sevoflurane; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D008738:Methyl Ethers; D016875:tau Proteins; D000077149:Sevoflurane