中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (1): 77-85.doi: 10.4103/1673-5374.224374

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

吗啡静脉自身给药改变小鼠大脑伏隔核miRNA表达谱

  

  • 收稿日期:2017-12-16 出版日期:2018-01-15 发布日期:2018-01-15
  • 基金资助:

    韩国政府科学和技术国家研究委员会基金；韩国国家研究基金

Intravenous morphine self-administration alters accumbal microRNA profiles in the mouse brain

Juhwan Kim1, 2, Heh-In Im2, 3, 4, Changjong Moon1   

  1. 1 Department of Veterinary Anatomy and Animal Behavior, College of Veterinary Medicine and BK21 Plus Project Team, Chonnam National University, Gwangju, South Korea
    2 Center for Neuroscience, Korea Institute of Science and Technology (KIST), Seoul, South Korea
    3 Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology (KIST), Seoul,South Korea
    4 Division of Biomedical Science & Technology, KIST School, Korea University of Science and Technology, Seoul, South Korea
  • Received:2017-12-16 Online:2018-01-15 Published:2018-01-15
  • Contact: Changjong Moon, D.V.M., M.S.,Ph.D. or Heh-In Im, D.V. M.,M.S., Ph.D.,moonc@chonnam.ac.kr or him@kist.re.kr.
  • Supported by:

    This research was funded by the National Research Council of Science & Technology (NST) grant by the Korean government (MSIP) (No. CRC-15-04-KIST) and the National Research Foundation of Korea under the grant (No. NRF-2017R1A2B200399; Mid-career Researcher Program).

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摘要：

大量的证据表明microRNAs（miRNAs）在药物成瘾中扮演着重要角色。伏隔核（NAc）是大脑奖赏回路的重要组成部分，参与包括抑郁、焦虑和药物成瘾在内的多种精神障碍的发病。为研究吗啡成瘾条件下miRNA在伏隔核中的表达及其功能作用，实验按0.01,0.03,0.3,1和3mg/kg剂量给予小鼠静脉注射吗啡，使其吗啡成瘾。利用微阵列分析吗啡静脉自身给药后伏隔核中miRNA表达谱，利用生物信息学工具“京都基因和基因组百科全书”（KEGG）通路制图和CyTargetLinker分析改变的miRNA功能网络及其标靶mRNA，发现62个miRNA表达发生改变，并表现出差异表达模式；同时发现了一些被这些miRNA调节的靶点，其与多种调节功能有关，如神经发生、神经变性和突触可塑性，以及吗啡的药理作用（受体内化/胞吞作用）。此研究结果为在吗啡成瘾条件下伏隔核miRNA参与的调节机制提供了新见解，并确定了几种与吗啡成瘾相关的新型生物标志物。

orcid:0000-0003-2451-0374(Changjong Moon)
0000-0002-4763-5009(Heh-In Im)

关键词: 神经再生, 伏隔核, miRNA, 吗啡, 自身给药, 生物信息学

Abstract:

A significant amount of evidence indicates that microRNAs (miRNAs) play an important role in drug addiction. The nucleus accumbens (NAc) is a critical part of the brain’s reward circuit and is involved in a variety of psychiatric disorders, including depression, anxiety, and drug addiction. However, few studies have examined the expression of miRNAs and their functional roles in the NAc under conditions of morphine addiction. In this study, mice were intravenously infused with morphine (0.01, 0.03, 0.3, 1 and 3 mg/kg/infusion) and showed inverted U-shaped response. After morphine self-administration, NAc was used to analyze the functional networks of altered miRNAs and their putative target mRNAs in the NAc following intravenous self-administration of morphine. We utilized several bioinformatics tools, including Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway mapping and CyTargetLinker. We found that 62 miRNAs were altered and exhibited differential expression patterns. The putative targets were related to diverse regulatory functions, such as neurogenesis, neurodegeneration, and synaptic plasticity, as well as the pharmacological effects of morphine (receptor internalization/endocytosis). The present findings provide novel insights into the regulatory mechanisms of accumbal molecules under conditions of morphine addiction and identify several novel biomarkers associated with morphine addiction.

Key words: nerve regeneration, nucleus accumbens, microRNA, morphine, self-administration, bioinformatics, neural regeneration