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Updated: May 19, 2026
Assessing Changes in Volatile General Anesthetic Sensitivity of Mice after Local or Systemic Pharmacological Intervention
Published on: October 16, 2013
Time-dependent repression of mPer2 expression in the suprachiasmatic nucleus by inhalation anesthesia with
Kana Kadota1, Norio Iijima, Yumiko Ohe-Hayashi
1Department of Anatomy and Neurobiology, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.
Abstract:
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.
Insights
Sevoflurane anesthesia represses mouse Per2 (mPer2) gene expression, particularly when administered in the morning. This effect impacts the circadian rhythm and may explain post-operative symptoms.
Area of Science:
- Neuroscience
- Chronobiology
- Pharmacology
Background:
- Anesthetics can alter gene expression, impacting biological rhythms.
- Sevoflurane anesthesia was previously shown to repress mouse Per2 (mPer2) gene expression in the suprachiasmatic nucleus (SCN).
Purpose of the Study:
- To investigate the time-dependent effects of sevoflurane anesthesia on mPer2 expression.
- To examine the interaction between sevoflurane anesthesia and the circadian rest/activity rhythm in mice.
Main Methods:
- Mice were exposed to sevoflurane anesthesia for 4 hours during specific times of the day.
- mPer2 expression in the SCN was quantified using in situ hybridization.
- Behavioral analysis assessed the impact on the rest/activity rhythm.
Main Results:
- Morning anesthesia exhibited the most significant repression of mPer2 expression.
- Sevoflurane repressed mPer2 expression under various light conditions, with light modifying the repression rate.
- Morning anesthesia led to mPer2 repression the subsequent day, suggesting an effect on transcription onset.
- Anesthesia induced a phase-delay in the rest/activity rhythm, but without time-dependency.
Conclusions:
- Sevoflurane anesthesia's impact on mPer2 expression is time-dependent, with morning administration being most potent.
- Anesthesia affects the circadian clock gene mPer2 and influences the rest/activity rhythm.
- Further research is needed to link these molecular changes to clinical symptoms like fatigue and sleep disturbances.
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