title: Characterization of sevoflurane effects on Per2 expression using ex vivo bioluminescence imaging of the suprachiasmatic nucleus in transgenic rats.
abstract: The inhalation anesthetic sevoflurane suppresses Per2 expression in the suprachiasmatic nucleus (SCN) in rodents. Here, we investigated the intra-SCN regional specificity, time-dependency, and pharmacological basis of sevoflurane-effects. Bioluminescence image was taken from the SCN explants of mPer2 promoter-destabilized luciferase transgenic rats, and each small regions of interest (ROI) of the image was analyzed. Sevoflurane suppressed bioluminescence in all ROIs, suggesting that all regions in the SCN are sensitive to sevoflurane. Clear time-dependency in sevoflurane effects were also observed; application during the trough phase of the bioluminescence cycle suppressed the subsequent increase in bioluminescence and resulted in a phase delay of the cycle; sevoflurane applied during the middle of the ascending phase induced a phase advance; sevoflurane on the descending phase showed no effect. These results indicate that the sevoflurane effect may depend on the intrinsic state of circadian machinery. Finally, we examined the involvement of GABAergic signal transduction in the sevoflurane effect. Co-application of both GABAA and GABAB receptor antagonists completely blocked the effect of sevoflurane on the bioluminescence rhythm, suggesting that sevoflurane inhibits Per2 expression via GABAergic signal transduction. Current study elucidated the anesthetic effects on the molecular mechanisms of circadian rhythm.
authors.affiliation: Department of Anatomy and Neurobiology, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan; Department of Anesthesiology and Pain Medicine, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.
authors.forename: Izumi
authors.initials: I
authors.lastname: Matsuo
authors.affiliation: Department of Anatomy and Neurobiology, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Iijima
authors.affiliation: Department of Anatomy and Neurobiology, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Takumi
authors.affiliation: Department of Anatomy and Neurobiology, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.
authors.forename: Shimpei
authors.initials: S
authors.lastname: Higo
authors.affiliation: Department of Anatomy and Neurobiology, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Aikawa
authors.affiliation: Department of Anesthesiology and Pain Medicine, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Anzai
authors.affiliation: Department of Anatomy and Neurobiology, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Ishii
authors.affiliation: Department of Anesthesiology and Pain Medicine, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Sakamoto
authors.affiliation: Department of Anatomy and Neurobiology, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan. Electronic address: hozawa@nms.ac.jp.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ozawa
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D058788:GABA-B Receptor Antagonists / Q000494:pharmacology; D008163:Luminescent Measurements; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D057054:Molecular Imaging; D056950:Period Circadian Proteins / Q000235:genetics / Q000378:metabolism*; D055647:Rats, Transgenic; D000077149:Sevoflurane; D013493:Suprachiasmatic Nucleus / Q000187:drug effects* / Q000378:metabolism
chemical_list: D018685:Anesthetics, Inhalation; D058787:GABA-A Receptor Antagonists; D058788:GABA-B Receptor Antagonists; D008738:Methyl Ethers; C513311:Per2 protein, rat; D056950:Period Circadian Proteins; D000077149:Sevoflurane
keywords: Circadian rhythm; Ex vivo bioluminescence imaging; GABA-receptors; Sevoflurane; Suprachiasmatic nucleus