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异氟醚暴露后 7 日龄小鼠齿状回中小 RNA/靶基因的鉴定。

Identification of microRNA/target gene in the dentate gyrus of 7‑day‑old mice following isoflurane exposure.

机构信息

Institute of Neurobiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China.

Institute of Neuroscience, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an, China.

出版信息

Acta Neurobiol Exp (Wars). 2022;82(1):96-105. doi: 10.55782/ane-2022-009.

DOI:10.55782/ane-2022-009
PMID:35451427
Abstract

Studies on rodents and nonhuman primates suggest that exposure to anesthetics, particularly in the young brain, is associated with neuronal apoptosis as well as hippocampal‑dependent cognitive dysfunction. Disruption of the development of dentate gyrus may play an important role in anesthetics‑induced neurotoxicity. However, the anesthetics triggered molecular events in the dentate gyrus of the developing brain are poorly understood. By integrating two independent data sets obtained from miRNA‑seq and mRNA‑seq respectively, this study aims to profile the network of miRNA and potential target genes, as well as relevant events occurring in the dentate gyrus of isoflurane exposed 7‑day‑old mice. We found that a single four hours exposure to isoflurane yielded 1059 pairs of differently expressed miRNAs/target genes in the dentate gyrus. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis further indicates that dysregulated miRNAs/target genes have far‑reaching effects on the cellular pathophysiological events, such as cell apoptosis, axon development, and synaptic transmission. Our results would greatly broaden our functional understanding of the role of miRNA/target gene in the context of anesthetics‑induced neurotoxicity.

摘要

啮齿动物和非人类灵长类动物的研究表明,接触麻醉剂,特别是在幼脑,与神经元凋亡以及海马依赖的认知功能障碍有关。齿状回发育中断可能在麻醉剂诱导的神经毒性中起重要作用。然而,在发育中的大脑齿状回中,麻醉剂引发的分子事件还知之甚少。通过整合分别从 miRNA-seq 和 mRNA-seq 获得的两个独立数据集,本研究旨在描绘 miRNA 和潜在靶基因的网络,以及异氟烷暴露 7 天大鼠齿状回中发生的相关事件。我们发现,单次 4 小时暴露于异氟烷会导致齿状回中 1059 对差异表达的 miRNA/靶基因。基因本体论和京都基因与基因组百科全书富集分析进一步表明,失调的 miRNA/靶基因对细胞病理生理事件(如细胞凋亡、轴突发育和突触传递)有深远的影响。我们的研究结果将极大地拓宽我们对 miRNA/靶基因在麻醉剂诱导的神经毒性中的作用的功能理解。

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