Direct and Specific Effect of Sevoflurane Anesthesia on rat Per2 Expression in the Suprachiasmatic Nucleus

Abstract

BackgroundOur previous studies revealed that application of the inhalation anesthetic, sevoflurane, reversibly repressed the expression of Per2 in the mouse suprachiasmatic nucleus (SCN). We aimed to examine whether sevoflurane directly affects the SCN.MethodsWe performed in vivo and in vitro experiments to investigate rat Per2 expression under sevoflurane-treatment. The in vivo effects of sevoflurane on rPer2 expression were examined by quantitative in situ hybridization with a radioactively-labeled cRNA probe. Additionally, we examined the effect of sevoflurane anesthesia on rest/activity rhythms in the rat. In the in vitro experiments, we applied sevoflurane to SCN explant cultures from Per2-dLuc transgenic rats, and monitored luciferase bioluminescence, representing Per2 promoter activity. Bioluminescence from two peripheral organs, the kidney cortex and the anterior pituitary gland, were also analyzed.ResultsApplication of sevoflurane in rats significantly suppressed Per2 expression in the SCN compared with untreated animals. We observed no sevoflurane-induced phase-shift in the rest/activity rhythms. In the in vitro experiments, the intermittent application of sevoflurane repressed the increase of Per2-dLuc luminescence and led to a phase delay in the Per2-dLuc luminescence rhythm. Sevoflurane treatment did not suppress bioluminescence in the kidney cortex or the anterior pituitary gland.ConclusionThe suppression of Per2-dLuc luminescence by sevoflurane in in vitro SCN cultures isolated from peripheral inputs and other nuclei suggest a direct action of sevoflurane on the SCN itself. That sevoflurane has no such effect on peripheral organs suggests that this action might be mediated through a neuron-specific cellular mechanism or a regulation of the signal transduction between neurons.

Day-Time Isoflurane Administration Suppresses Circadian Gene Expressions in Both the Brain and a Peripheral Organ, Liver

“…In contrast with our findings, Anzai et al (17) failed to show the effect of sevoflurane on gene expression in peripheral organs, although they reported suppression in PER2 expression in SCN. The difference between these two studies may be arise from the difference in volatile agents or peripheral organs.…”

Epigenetic Suppression of Mouse Per2 Expression in the Suprachiasmatic Nucleus by the Inhalational Anesthetic, Sevoflurane

“…In this study, we aimed to elucidate the molecular mechanism of this suppression. Our previous in vitro study using Per2-dLuc transgenic rats showed that sevoflurane suppressed mouse Per2 promoter-driven luciferase expression, indicating that it acts by modulating the Per2 promoter [8]. We focused here on the epigenetic events occurring in the Per2 promoter in the SCN under anesthesia because it is well known that Per2 expression is controlled by the balance between histone acetylation and deacetylation [11], [14].…”

“…Quantitative in situ hybridization revealed that sevoflurane anesthesia reversibly suppressed Per2 expression in the SCN of rats and mice [7], [8]. Application of sevoflurane to an SCN slice culture taken from transgenic rats expressing a mouse Per2 promoter-destabilized luciferase ( Per2-dLuc ) revealed that suppression of bioluminescence led to a phase delay in the bioluminescence rhythm.…”

Sevoflurane downregulates interleukin-6 and interleukin-8 levels in patients after cardiopulmonary bypass surgery: a meta-analysis

“…Further, both pre-and post-treatment of sevoflurane have protective myocardial effects (Anzai et al, 2013).There are significant differences between pretreatment and post-treatment of sevoflurane because of its in vivo mechanisms. With the opening of the ATP-sensitive potassium channel, pretreatment of sevoflurane may contribute to an increased mitochondrial matrix volume and maintenance of the integrity of mitochondria, and eventually exerting its effects on myocardial protection (Bouwman et al, 2007;Onishi et al, 2012).…”