The general anesthetic sevoflurane affects the expression of clock gene mPer2 accompanying the change of NAD+ level in the suprachiasmatic nucleus of mice

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.

Research highlights▶ Sevoflurane exhibited repression on the light-induced mPer2 expression in the SCN. ▶ mPer2 expression was repressed after anesthesia on the circadian cycle in the SCN. ▶ This repression was observed in subsequent phases of expression cycles. ▶ The phase-delay of the circadian rhythm in locomotive activity was detected. ▶ The increase of NAD+ with anesthesia was clearly observed.