title: Direct and specific effect of sevoflurane anesthesia on rat Per2 expression in the suprachiasmatic nucleus.
abstract: BACKGROUND
  Our previous studies revealed that application of the inhalation anesthetic, sevoflurane, reversibly repressed the expression of Per2 in the mouse suprachiasmatic nucleus (SCN). We aimed to examine whether sevoflurane directly affects the SCN.
  
  
  METHODS
  We performed in vivo and in vitro experiments to investigate rat Per2 expression under sevoflurane-treatment. The in vivo effects of sevoflurane on rPer2 expression were examined by quantitative in situ hybridization with a radioactively-labeled cRNA probe. Additionally, we examined the effect of sevoflurane anesthesia on rest/activity rhythms in the rat. In the in vitro experiments, we applied sevoflurane to SCN explant cultures from Per2-dLuc transgenic rats, and monitored luciferase bioluminescence, representing Per2 promoter activity. Bioluminescence from two peripheral organs, the kidney cortex and the anterior pituitary gland, were also analyzed.
  
  
  RESULTS
  Application of sevoflurane in rats significantly suppressed Per2 expression in the SCN compared with untreated animals. We observed no sevoflurane-induced phase-shift in the rest/activity rhythms. In the in vitro experiments, the intermittent application of sevoflurane repressed the increase of Per2-dLuc luminescence and led to a phase delay in the Per2-dLuc luminescence rhythm. Sevoflurane treatment did not suppress bioluminescence in the kidney cortex or the anterior pituitary gland.
  
  
  CONCLUSIONS
  The suppression of Per2-dLuc luminescence by sevoflurane in in vitro SCN cultures isolated from peripheral inputs and other nuclei suggest a direct action of sevoflurane on the SCN itself. That sevoflurane has no such effect on peripheral organs suggests that this action might be mediated through a neuron-specific cellular mechanism or a regulation of the signal transduction between neurons.
authors.affiliation: Department of Anatomy and Neurobiology, Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Anzai
authors.forename: Norio
authors.initials: N
authors.lastname: Iijima
authors.forename: Shimpei
authors.initials: S
authors.lastname: Higo
authors.forename: Ken
authors.initials: K
authors.lastname: Takumi
authors.forename: Izumi
authors.initials: I
authors.lastname: Matsuo
authors.forename: Keisuke
authors.initials: K
authors.lastname: Mori
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Ohe
authors.forename: Kana
authors.initials: K
authors.lastname: Kadota
authors.forename: Toshio
authors.initials: T
authors.lastname: Akimoto
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Sakamoto
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ozawa
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism; D056950:Period Circadian Proteins / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D012146:Rest / Q000502:physiology; D000077149:Sevoflurane; D013493:Suprachiasmatic Nucleus / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; C513311:Per2 protein, rat; D056950:Period Circadian Proteins; D000077149:Sevoflurane; D010100:Oxygen
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