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

Goto, Gentaro; Hori, Yoko; Ishikawa, Masashi; Tanaka, Shunsuke; Sakamoto, Atsuhiro

doi:10.3892/mmr.2014.2038

Cited by 38 publications

(28 citation statements)

References 38 publications

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“…The reasons underlying the difference between their results and those of the present study remain to be elucidated. However, one notable difference is that Goto et al (14) conducted experiments on 6-week-old male Wistar rats, whereas 7-day-old Sprague-Dawley rats were employed in the current study. Previous studies have demonstrated that ketamine leads to neuroapoptosis in the developing brain (26), and that miR-34a negatively regulates ketamine-induced apoptosis in the hippocampus (15).…”

Section: Discussionmentioning

confidence: 98%

“…Therefore, miR34c was selected for further investigation. Notably, Goto et al (14) reported a contrasting result. In this previous study, 4 miRNAs were observed to be significantly increased, while 12 miRNAs were significantly reduced in the rat hippocampus following sevoflurane anesthesia.…”

Section: Discussionmentioning

confidence: 98%

“…MicroRNAs (miRNAs/miRs) are small non-coding RNAs that serve as regulators of endogenous epigenetic gene expression, and serve important roles in multiple physiological/pathological processes, such as cell death and survival (12,13). A recent study demonstrated that sevoflurane combined with propofol anesthesia may lead to alterations in expression levels of miRNAs in the hippocampus of rats (14). In addition, miR-34a has been demonstrated to be involved in ketamine-induced hippocampal apoptosis (15).…”

Section: Introductionmentioning

confidence: 99%

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MicroRNA-34c is regulated by p53 and is involved in sevoflurane-induced apoptosis in the developing rat brain potentially via the mitochondrial pathway

Zhou

Xian

Xia

et al. 2017

Molecular Medicine Reports

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The commonly used inhalation anesthetic, sevoflurane, has been previously demonstrated to induce apoptosis in the developing brain; however, the underlying molecular mechanisms remain largely unknown. MicroRNAs (miRNAs) serve important roles in multiple physiological/pathological processes, such as cell death and survival. In the present study, the miRNA sequence that was most closely associated with sevoflurane-induced apoptosis in the hippocampus of neonatal rat brains was identified. Seven-day-old Sprague Dawley rats were first exposed to 2.3% sevoflurane for 6 h. Hippocampal brain tissues were harvested at 6 h following sevoflurane exposure. Cleaved caspase-3 levels were examined using an immunofluorescence assay. Alterations in miRNA expression were assessed by microarray analysis and reverse transcription-quantitative polymerase chain reaction. The protein levels of p53, phosphorylated (p)-p53, B-cell lymphoma-2 (Bcl-2) and Bax were assessed by western blot analysis. Sevoflurane exposure significantly increased the levels of cleaved caspase-3 in the hippocampus. In addition, among the 688 miRNAs that were observed to be expressed in the hippocampus, sevoflurane exposure altered the expression levels of 266 miRNAs. Among these differentially expressed miRNAs, eight were significantly upregulated and one (miRNA-34c) was significantly downregulated following sevoflurane exposure. Bioinformatics analyses indicated the miRNA-34c was a direct downstream target of p53. Sevoflurane exposure induced significant alterations in the level of p-p53, Bcl-2 and Bax in the hippocampus of neonatal rats. In conclusion, the results of the present study suggest that miRNA-34c may be regulated by p53 and is involved in sevoflurane-induced neural apoptosis in the hippocampus of developing rat brains, potentially via the mitochondrial pathway.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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MicroRNA-34c is regulated by p53 and is involved in sevoflurane-induced apoptosis in the developing rat brain potentially via the mitochondrial pathway

Zhou

Xian

Xia

et al. 2017

Molecular Medicine Reports

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“…A similar dose was also used in previous studies (40,41). None of these pups appeared to undergo hypoxemia or hypocapnia during the sevoflurane exposure for 4 h, as verified by their arterial blood analysis.…”

Section: Discussionmentioning

confidence: 99%

Altered hippocampal microRNA expression profiles in neonatal rats caused by sevoflurane anesthesia: MicroRNA profiling and bioinformatics target analysis

Zhang

Wang

et al. 2016

Experimental and Therapeutic Medicine

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Although accumulating evidence has suggested that microRNAs (miRNAs) have a serious impact on cognitive function and are associated with the etiology of several neuropsychiatric disorders, their expression in sevoflurane-induced neurotoxicity in the developing brain has not been characterized. In the present study, the miRNAs expression pattern in neonatal hippocampus samples (24 h after sevoflurane exposure) was investigated and 9 miRNAs were selected, which were associated with brain development and cognition in order to perform a bioinformatic analysis. Previous microfluidic chip assay had detected 29 upregulated and 24 downregulated miRNAs in the neonatal rat hippocampus, of which 7 selected deregulated miRNAs were identified by the quantitative polymerase chain reaction. A total of 85 targets of selected deregulated miRNAs were analyzed using bioinformatics and the main enriched metabolic pathways, mitogen-activated protein kinase and Wnt pathways may have been involved in molecular mechanisms with regard to neuronal cell body, dendrite and synapse. The observations of the present study provided a novel understanding regarding the regulatory mechanism of miRNAs underlying sevoflurane-induced neurotoxicity, therefore benefitting the improvement of the prevention and treatment strategies of volatile anesthetics related neurotoxicity.

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“…miRNA microchip technology provides for simultaneous detection of the global expression of several hundred miRNAs in a single sample, and it has been previously used to characterize the miRNA transcriptomic signatures of anesthetic agents in the liver (Ishikawa et al, 2012) and hippocampus (Goto et al, 2014). Here, we used miRNA microchips and quantitative real-time polymerase chain reaction (qRT-PCR) to characterize the effect of lowand high-dosage propofol on miRNA expression patterns in primary cultures of hippocampal astrocytes isolated from immature rats.…”

mentioning

confidence: 99%

microRNA Expression Profiling of Propofol-Treated Developing Rat Hippocampal Astrocytes

Sun

Pei

2015

DNA and Cell Biology

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Although propofol exerts toxic effects on the developing central nervous system (CNS), it remains a first-choice anesthetic in the pediatric population. Astrocytes represent a major glial cell population whose role in CNS development is widely appreciated and that has been recently shown to be mediated in large part by microRNAs (miRNAs). In contrast, relatively little is known about the roles of miRNAs in developing astrocytes during propofol treatment. Here, miRNA microarray was used to profile fluctuations in miRNA expression in immature hippocampal astrocytes in response to propofol treatment, and results were subsequently validated using quantitative real-time polymerase chain reaction. Predictive analysis of genes targeted by propofol-regulated miRNAs indicated enrichment of genes in the gene ontology (GO) nervous system development and differentiation category, and in the Kyoto encyclopedia of genes and genomes (KEGG) apoptotic pathway category. A total of 24 (10 short-term dosage and 14 long-term dosage) miRNAs were significantly regulated, one of which was rno-miR-665. Ectopic overexpression and silencing of rno-miR-665 demonstrated its role in the neurotoxic effects of propofol on hippocampal immature astrocytes. We present evidence that the role of rnomiR-665 in anesthesia-induced disturbances in astroglia development may involve direct downregulation of the anti-apoptotic gene Bcl2l1, and subsequent increased caspase-3-mediated apoptosis. Our results shed light on the anesthetic mechanism of propofol and have implications for its use in the clinical setting.

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

Cited by 38 publications

References 38 publications

MicroRNA-34c is regulated by p53 and is involved in sevoflurane-induced apoptosis in the developing rat brain potentially via the mitochondrial pathway

MicroRNA-34c is regulated by p53 and is involved in sevoflurane-induced apoptosis in the developing rat brain potentially via the mitochondrial pathway

Altered hippocampal microRNA expression profiles in neonatal rats caused by sevoflurane anesthesia: MicroRNA profiling and bioinformatics target analysis

microRNA Expression Profiling of Propofol-Treated Developing Rat Hippocampal Astrocytes

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