Time-dependent repression of mPer2 expression in the suprachiasmatic nucleus by inhalation anesthesia with sevoflurane.
Some anesthetics can affect gene expression. Previously, we reported that sevoflurane anesthesia drastically and reversibly repressed the expression of mouse Per2 (mPer2), a core clock gene in the suprachiasmatic nucleus (SCN). In the current study, we examined the time-dependent effect of sevoflurane on mPer2 expression and its interactions with the circadian rest/activity rhythm of mice. During certain hours of the day, mice were anesthetized with 2.5% sevoflurane in 40% oxygen for 4h. The expression level of mPer2 in the SCN was measured by in situ hybridization using a radiolabeled cRNA probe. Anesthesia during the morning hours showed the greatest repressive effect on mPer2 expression. Sevoflurane anesthesia repressed mPer2 expression during the conditions of light/dark and constant dark, and the light conditions modified the repression rate under anesthesia. Moreover, anesthesia in the morning also repressed mPer2 expression the following day. This dominant effect of anesthesia in the morning indicates that sevoflurane anesthesia affects the onset of mPer2 transcription. Behavior analysis revealed that the anesthetic treatment also induced a phase-delay in the rest/activity rhythm. However, no time-dependent effects of anesthesia on the circadian rest/activity rhythm were observed. Further investigation into the molecular events caused by anesthesia are required to explain atypical clinical signs observed in patients after surgical procedures, such as fatigue, sleep disorder, mood alteration and delirium.
Department of Anatomy and Neurobiology, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.
Kana
K
Kadota
Norio
N
Iijima
Yumiko
Y
Ohe-Hayashi
Ken
K
Takumi
Shimpei
S
Higo
Atsuhiro
A
Sakamoto
Hitoshi
H
Ozawa
D018685:Anesthetics, Inhalation / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D002940:Circadian Rhythm; D008297:Male; D008738:Methyl Ethers / Q000009:adverse effects / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D056950:Period Circadian Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012146:Rest; D000077149:Sevoflurane; D013493:Suprachiasmatic Nucleus / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D000077149:Sevoflurane