title: The general anesthetic sevoflurane affects the expression of clock gene mPer2 accompanying the change of NAD+ level in the suprachiasmatic nucleus of mice.
abstract: Sevoflurane is an anesthetic for the general anesthesia. In this study, we showed that sevoflurane anesthesia affects the expression of mouse Per2 (mPer2), which is a clock gene in the brain which is considered the organ where the anesthetics act in. 64.5% of mPer2 circadian expression was repressed under anesthesia in the suprachiasmatic nucleus (SCN) of the brain. After recovering from the anesthesia, the repressed mPer2 expression was restored to the same level as in non anesthesia-treated mice. This repression pattern was also observed in the subsequent phases of diurnal mPer2 expression. However, obvious phase-shift in the mPer2 expression was not showed in this study. On the other hand, the behavior analysis in this experiment exhibited that the phases in the circadian behavioral rhythm were shifted backwards. We also measured the NAD(+) level in the SCN, which was a mediator regulating the mPer2 expression. Then, significant increase of NAD(+) was detected under the anesthesia. These results indicate that the anesthesia induces the increase of NAD(+), and consequently leads to the repression of mPer2 expression and modifies the circadian expression pattern and diurnal behavioral rhythm of mice. Furthermore, the modification of mPer2 expression by the anesthesia is considered to affect various gene expressions.
authors.affiliation: Department of Anatomy and Neurobiology, Graduate School of Medicine, Nippon Medical School, Sendagi 1-1-5, Bunkyo-ku, Tokyo 113-8602, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Ohe
authors.forename: Norio
authors.initials: N
authors.lastname: Iijima
authors.forename: Kana
authors.initials: K
authors.lastname: Kadota
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; D002940:Circadian Rhythm / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D008027:Light; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009243:NAD / Q000378:metabolism*; D056950:Period Circadian Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger; D000077149:Sevoflurane; D013493:Suprachiasmatic Nucleus / Q000187:drug effects*; D013997:Time Factors
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D012333:RNA, Messenger; D009243:NAD; D000077149:Sevoflurane