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

View Article: PubMed Central - PubMed

ABSTRACT

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.

No MeSH data available.


Categories and distribution of the gene ontology terms of predicted targets for nine miRNAs. In the biological process, significant target genes were distributed in the regulation of transcription, DNA-dependency, response to drug, ion transport, multicellular organismal development, positive regulation of transcription from RNA, polymerase II promoter and signal transduction. In the field of the cellular component, genes are enriched in the cytoplasm, nucleus, integral to membrane, membrane, plasma membrane, mitochondrion, nucleolus, endoplasmic reticulum, intracellular part and the cytosol. For the molecular function, the major significant genes are enriched in nucleotide, protein, ATP, metal ion, DNA, zinc ion binding, and transferase and receptor activity. ☆Regulation of transcription, DNA-dependency, ★multicellular organismal development. ◆Positive regulation of transcription from RNA polymerase II promoter. miRNA, microRNA; ATP, adenosine triphosphate.
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f3-etm-0-0-3452: Categories and distribution of the gene ontology terms of predicted targets for nine miRNAs. In the biological process, significant target genes were distributed in the regulation of transcription, DNA-dependency, response to drug, ion transport, multicellular organismal development, positive regulation of transcription from RNA, polymerase II promoter and signal transduction. In the field of the cellular component, genes are enriched in the cytoplasm, nucleus, integral to membrane, membrane, plasma membrane, mitochondrion, nucleolus, endoplasmic reticulum, intracellular part and the cytosol. For the molecular function, the major significant genes are enriched in nucleotide, protein, ATP, metal ion, DNA, zinc ion binding, and transferase and receptor activity. ☆Regulation of transcription, DNA-dependency, ★multicellular organismal development. ◆Positive regulation of transcription from RNA polymerase II promoter. miRNA, microRNA; ATP, adenosine triphosphate.

Mentions: With the use of GO (Gene ontology; http://amigo.geneontology.org/amigo), these putative miRNA targets can be used as an input in order to perform the GO functional enrichment. From the enrichment results, the main 27 GO terms are shown in Fig. 3. These results could demonstrate that the target genes of nine miRNAs in neonatal rats' hippocampus are involved in a wide variety of pathophysiological processes after sevoflurane exposure. In order to explore the possible mechanism of neurotoxicity induced by sevoflurane, 19 GO terms were selected that were thought to be associated to brain development and cognition among the ~3,200 GO terms of the nine miRNAs (Table V). The most significant GOs associated with the nine cognition-related miRNAs included the neuronal cell body (GO:0043025), dendrite (GO:0030425) and synapse (GO:0045202).


Altered hippocampal microRNA expression profiles in neonatal rats caused by sevoflurane anesthesia: MicroRNA profiling and bioinformatics target analysis
Categories and distribution of the gene ontology terms of predicted targets for nine miRNAs. In the biological process, significant target genes were distributed in the regulation of transcription, DNA-dependency, response to drug, ion transport, multicellular organismal development, positive regulation of transcription from RNA, polymerase II promoter and signal transduction. In the field of the cellular component, genes are enriched in the cytoplasm, nucleus, integral to membrane, membrane, plasma membrane, mitochondrion, nucleolus, endoplasmic reticulum, intracellular part and the cytosol. For the molecular function, the major significant genes are enriched in nucleotide, protein, ATP, metal ion, DNA, zinc ion binding, and transferase and receptor activity. ☆Regulation of transcription, DNA-dependency, ★multicellular organismal development. ◆Positive regulation of transcription from RNA polymerase II promoter. miRNA, microRNA; ATP, adenosine triphosphate.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4998092&req=5

f3-etm-0-0-3452: Categories and distribution of the gene ontology terms of predicted targets for nine miRNAs. In the biological process, significant target genes were distributed in the regulation of transcription, DNA-dependency, response to drug, ion transport, multicellular organismal development, positive regulation of transcription from RNA, polymerase II promoter and signal transduction. In the field of the cellular component, genes are enriched in the cytoplasm, nucleus, integral to membrane, membrane, plasma membrane, mitochondrion, nucleolus, endoplasmic reticulum, intracellular part and the cytosol. For the molecular function, the major significant genes are enriched in nucleotide, protein, ATP, metal ion, DNA, zinc ion binding, and transferase and receptor activity. ☆Regulation of transcription, DNA-dependency, ★multicellular organismal development. ◆Positive regulation of transcription from RNA polymerase II promoter. miRNA, microRNA; ATP, adenosine triphosphate.
Mentions: With the use of GO (Gene ontology; http://amigo.geneontology.org/amigo), these putative miRNA targets can be used as an input in order to perform the GO functional enrichment. From the enrichment results, the main 27 GO terms are shown in Fig. 3. These results could demonstrate that the target genes of nine miRNAs in neonatal rats' hippocampus are involved in a wide variety of pathophysiological processes after sevoflurane exposure. In order to explore the possible mechanism of neurotoxicity induced by sevoflurane, 19 GO terms were selected that were thought to be associated to brain development and cognition among the ~3,200 GO terms of the nine miRNAs (Table V). The most significant GOs associated with the nine cognition-related miRNAs included the neuronal cell body (GO:0043025), dendrite (GO:0030425) and synapse (GO:0045202).

View Article: PubMed Central - PubMed

ABSTRACT

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.

No MeSH data available.