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注意缺陷多动障碍大鼠海马中的 microRNA 谱分析。

miRNA profiling in the hippocampus of attention-deficit/hyperactivity disorder rats.

机构信息

Department of Child Health Care, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Department of Pediatrics, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical College, The Affiliated XuZhou Hospital of Medical College of Southeast University, Jiangsu, China.

出版信息

J Cell Biochem. 2019 Mar;120(3):3621-3629. doi: 10.1002/jcb.27639. Epub 2018 Sep 30.

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is characterized by attention  deficit, hyperactivity, impulsivity, and learning and memory impairment. Although the pathogenesis of learning and memory impairment is still unknown, some studies have suggested an association with hippocampus dysfunction. We aimed to explore the role of miRNAs in the learning and memory impairments observed in ADHD. Differentially expressed hippocampal micro-ribonucleic acids (miRNAs) in spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats (WKYs) were detected on an Illumina HiSeq. 2000 genome analyzer. A total of 25 differentially expressed miRNAs (fold-change ≥ 2 and P-value < 0.05) were identified. The target genes of these differentially expressed miRNAs were predicted using online tools (TargetScan and miRDB). Gene ontology and pathway analysis of the predicted target genes were carried out to assess their putative biological functions. Meanwhile, quantitative real-time PCR was used to validate the HiSeq results, revealing that three miRNAs (miR-1-b, miR-741-3p, and miR-206-3p) were upregulated and four (miR-182, miR-471-5p, miR-183-5p, and miR-211-5p) were downregulated in the SHR group compared with the WKY group. In addition, we confirmed that Dyrk1a is regulated by miR-211-5p. These results help us understand the contribution of miRNAs in the hippocampus to ADHD and provide new insights into the pathogenesis of this condition.

摘要

注意缺陷多动障碍(ADHD)的特征为注意力缺陷、多动、冲动以及学习和记忆损伤。虽然学习和记忆损伤的发病机制仍不清楚,但一些研究提示其与海马功能障碍有关。我们旨在探讨 microRNAs 在 ADHD 观察到的学习和记忆损伤中的作用。在自发性高血压大鼠(SHRs)和 Wistar-Kyoto 大鼠(WKYs)的海马中,通过 Illumina HiSeq. 2000 基因组分析仪检测到差异表达的 micro-ribonucleic acids(miRNAs)。鉴定出 25 个差异表达的 miRNAs(fold-change≥2 且 P 值<0.05)。使用在线工具(TargetScan 和 miRDB)预测这些差异表达 miRNAs 的靶基因。对预测靶基因进行基因本体和通路分析,以评估其可能的生物学功能。同时,使用定量实时 PCR 验证 HiSeq 结果,显示 miR-1-b、miR-741-3p 和 miR-206-3p 这 3 个 miRNA 上调,miR-182、miR-471-5p、miR-183-5p 和 miR-211-5p 这 4 个 miRNA 下调。此外,我们证实 Dyrk1a 受 miR-211-5p 调控。这些结果有助于我们了解 miRNA 在海马体对 ADHD 的贡献,并为该病的发病机制提供新的见解。

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