Differences in recovery processes of circadian oscillators in various tissues after sevoflurane treatment in vivo

The inhalation anesthetic sevoflurane reversibly suppresses Period2 (Per2) mRNA expression in the suprachiasmatic nucleus (SCN). However, a discrepancy exists in phase shifting of the Per2 expression rhythm between sevoflurane application in rats (in vivo application) and explants (ex vivo application). This investigation aimed to resolve this issue. First, tissues from the SCN, choroid plexus in the lateral ventricle (CP-LV), and choroid plexus in the fourth ventricle (CP–4V), which are robust circadian oscillators, and pineal gland (PG) tissue, which is a circadian influencer, were prepared from Per2::dLuc transgenic rats. Significant phase responses of bioluminescence rhythms for different preparation times were monitored in the four tissue explant types. Second, tissue explants were prepared from anesthetized rats immediately after sevoflurane treatment, and bioluminescence rhythms were compared with those from non-anesthetized rats at various preparation times. Regarding bioluminescence rhythm phases, in vivo application of sevoflurane induced phase shifts in CP-LV, CP-4V, and PG explants according to the times that rats were administered anesthesia and the explants were prepared. Phase shifts in these peripheral explants were withdrawn due to the recovery period after the anesthetic treatment, which suggests that peripheral tissues require the assistance of related tissues or organs to correct phase shifts. In contrast, no phase shifts were observed in SCN explants. These results indicated that SCN explants can independently correct bioluminescence rhythm phase. The bioluminescence intensity of explants was also decreased after in vivo sevoflurane application. The suppressive effects on SCN explants were withdrawn due to a recovery day after the anesthetic treatment. In contrast, the suppressive effects on the bioluminescence intensities of CP-LV, CP-4V, and PG explants remained at 30 days after anesthesia administration. These results suggest that anesthetic suppression is imprinted within the peripheral tissues.