Circadian gene expression is suppressed during sevoflurane anesthesia and the suppression persists after awakening

Kobayashi, Katsuya; Takemori, Ken; Sakamoto, Atsuhiro

doi:10.1016/j.brainres.2007.09.011

Cited by 36 publications

(31 citation statements)

References 38 publications

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“…In a previous genomic study, the inhalation anesthetic sevoflurane affected the expression of 1.5% of genes in various rat organs, as detected using a microarray analysis (7). General anesthesia altered the expression levels of genes involved in circadian rhythms; persistent suppression of several circadian genes was identified following treatment of rats with the inhalation anesthetic sevoflurane (8) and the intravenous anesthetics propofol and dexmedetomidine (9). In a proteomics study, the protein expression in the rat brain was regulated differentially according to the anesthetic agent used: The inhalation anesthetic sevoflurane or the intravenous anesthetic propofol (10).…”

Section: Introductionmentioning

confidence: 94%

Changes in the gene expression levels of microRNAs in the rat hippocampus by sevoflurane and propofol anesthesia

Goto

Hori

Ishikawa

et al. 2014

Molecular Medicine Reports

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Abstract. General anesthesia is commonly used in the surgical arena, but little is known regarding its influence at the genomic and molecular levels. MicroRNAs (miRNAs) belong to a new class of non-coding RNA molecules which influence cell biology. In the present study, it was hypothesized that miRNAs alter gene expression levels under general anesthesia. The aim was to compare the miRNA expression profiles in the rat hippocampus in response to anesthesia with representative volatile (sevoflurane) and intravenous (propofol) anesthetics. Wistar Rats were randomly assigned to either a 2.4% sevoflurane, 600 µg/kg/min propofol or control (without anesthetics) group. Total RNA from hippocampal samples which contained miRNA was subjected to quantitative reverse transcriptionpolymerase chain reaction and Taqman Low-Density Arrays (TLDA). A total of 373 miRNAs are associated with rats and the TLDA analysis revealed that 279 expressed miRNAs (74.8%) were expressed in all three groups. Significant differences in the levels of 33 of the 279 expressed miRNAs (11.8%) were observed among the three groups in response to the anesthetic agents, and when compared with the control group, significant differences were found in 26 of the 279 expressed miRNAs (9.3%). Following sevoflurane anesthesia, the levels of four miRNAs were significantly increased and those of 12 were significantly reduced. By contrast, following propofol anesthesia, the levels of 11 miRNAs were significantly reduced but no miRNAs exhibited significantly elevated levels. Fourteen miRNAs were significantly differentially expressed between the two anesthesia groups. In conclusion, sevoflurane and propofol exerted different effects on miRNA expression in the rat hippocampus.

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Section: Introductionmentioning

confidence: 94%

Changes in the gene expression levels of microRNAs in the rat hippocampus by sevoflurane and propofol anesthesia

Goto

Hori

Ishikawa

et al. 2014

Molecular Medicine Reports

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“…Several studies indicated that general anaesthesia regulates the expression of many genes in the brain and other organs such as blood, heart and lung (4-6). Kobayashi et al (7) showed that the expression of several circadian genes including PER2 (period homolog 2) was suppressed during inhalation of sevoflurane for two hours and six hours in rat whole brain. Yoshida et al (8) found that propofol administration significantly changes the expression of circadian genes in rat whole brain, and the influence of intravenous anaesthesia also persists for 24 hours after awakening from anaesthesia.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies investigated the effect of the administration of anaesthetics on circadian gene expression in mammalian organisms (mice and rats) (7,(13)(14)(15). All these studies investigated circadian gene expression 2, 6 or 24 hours after administration.…”

Section: Discussionmentioning

confidence: 99%

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

Gökmen¹,

Barış²,

Öçmen³

et al. 2017

Turk J Anaesth Reanim

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“…Eliminating any spots resulting from in-gel trypsin digestion, propofol anaesthesia altered the levels of 39 proteins in the cerebral proteome, with sixteen of these being up-regulated and twenty-three proteins down-regulated. In contrast, sevoflurane anaesthesia altered the levels of 58 procomparison with propofol because it is one of the most commonly used inhaled clinical anaesthetic agents, and we have used it extensively in our previous genomic studies on the effects of anaesthetics on gene expression in the brain (20,37,41). Propofol produces a hypnotic effect by potentiating the gamma-aminobutyric acid-induced chloride current by binding to the beta-subunit of the GABA A receptor (15,32,38).…”

Section: Discussionmentioning

confidence: 99%

“…A number of genomic studies have been published, and we have shown that general anaesthesia alters gene expression, especially expression of genes involved in circadian rhythms and drug metabolism. For instance, we found persistent suppression of the expression of several genes implicated in circadian rhythms (e.g., Per2, Dbp, Egr1, Krox20 and NGF1-B) following treatment of rats with sevoflurane (20) and propofol or dexmedetomidine (41). We have also reported changes in the expression of drug metabolising enzymes in rats (e.g., Cyp2b15, Por, Nr1i2, Ces2, Ugt1a7, Abcb1a and Abcc2) in response to sevoflurane, isoflurane, propofol, or dexmedetomidine anaesthesia (30,37) The observed changes varied depending on the identity of the anaesthetic used, and also on the mode of administration (inhaled vs. intravenous).…”

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confidence: 89%

Propofol anaesthesia alters the cerebral proteome differently from sevoflurane anaesthesia

Tsuboko

Sakamoto

2011

Biomed. Res.

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Previous studies suggest that propofol and sevoflurane anaesthesia in rats may have variable effects on the proteome. Brains from untreated rats and rats anaesthetised with intravenous propofol infusion or inhaled sevoflurane were collected at various time points post-anaesthesia and subjected to global protein expression profiling using two-dimensional gel electrophoresis. Significant changes in protein spot intensity (i.e. expression) between the propofol and sevoflurane groups demonstrated clear similarities and differences in proteomic regulation by these anaesthetics. The proteins regulated were broadly classified into groups involved in cytoskeletal/neuronal growth, cellular metabolism, signalling, and cell stress/death responses. Proteins concerned with cell death and stress responses were down-regulated by both agents, but the anaesthetics had variable effects on proteins in the other groups. Importantly, proteins such as Ulip2 and dihydropyrimidinaselike-2 were regulated in opposite directions by propofol and sevoflurane. Moreover, the timecourse of regulation of proteins varied depending on the agent used. These data suggest different underlying mechanisms of proteomic regulation. We found that sevoflurane anaesthesia had more pronounced effects, on a wider range of proteins, and over an apparently longer duration than propofol. Thus, sevoflurane could be considered a more disruptive anaesthetic agent. Our findings show that protein expression is regulated differentially according to the anaesthetic agent and the method of delivery support and extend our previous observations of differential genomic regulation by anaesthetics in the brain. This study highlights the power of proteomic studies in assessing the effects of certain anaesthetics on the integrity of neuronal structure and function.The utility of general anaesthetics is unquestioned, and their harmlessness with regard to mortality and morbidity has been evaluated and endorsed by clinical outcomes (3,(10)(11)(12)24). Little is known, however, regarding their comprehensive influence at the genomic or proteomic level, which is not reflected in mortality and morbidity. A number of genomic studies have been published, and we have shown that general anaesthesia alters gene expression, especially expression of genes involved in circadian rhythms and drug metabolism. For instance, we found persistent suppression of the expression of several genes implicated in circadian rhythms (e.g., Per2, Dbp, Egr1, Krox20 and NGF1-B) following treatment of rats with sevoflurane (20) and propofol or dexmedetomidine (41). We have also reported changes in the expression of drug metabolising enzymes in rats (e.g., Cyp2b15, Por, Nr1i2, Ces2, Ugt1a7, Abcb1a and Abcc2) in response to sevoflurane, isoflurane, propofol, or dexmedetomidine anaesthesia (30, 37) The observed changes varied depending on the identity of the anaesthetic used, and also on the mode of administration (inhaled vs. intravenous). Therefore, it is clear that anaesthetics have significant effects...

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Circadian gene expression is suppressed during sevoflurane anesthesia and the suppression persists after awakening

Cited by 36 publications

References 38 publications

Changes in the gene expression levels of microRNAs in the rat hippocampus by sevoflurane and propofol anesthesia

Changes in the gene expression levels of microRNAs in the rat hippocampus by sevoflurane and propofol anesthesia

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

Propofol anaesthesia alters the cerebral proteome differently from sevoflurane anaesthesia

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