Methamphetamine leads to the alterations of microRNA profiles in the nucleus accumbens of rats.
Methamphetamine leads to the alterations of microRNA profiles in the nucleus accumbens of rats.
复制标题
甲基苯丙胺导致大鼠伏核中 microRNA 谱的改变
DOI：
10.1080/13880209.2020.1803366
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发表时间：
2020-12
影响因子：
3.8
通讯作者：
Zhou Y
中科院分区：
文献类型：
--
作者：
Yang J;Li L;Hong S;Zhang D;Zhou Y
摘要背景microRNA（miRNA）是基因表达的重要调控因子。甲基苯丙胺（METH）通过影响基因表达在不同系统中诱导各种改变，但METH对miRNA谱的影响需要阐明。目的建立甲基苯丙胺（METH）成瘾大鼠模型，并分析甲基苯丙胺成瘾大鼠中脑延髓核（NAc）内miRNA表达谱的变化。材料和方法Sprague-Dawley大鼠每天两次给予10 mg/kg METH或溶媒，持续4周。通过CPP试验评价大鼠的成瘾行为。采用HE和Glee银染色观察脑组织病理变化。使用Illumina HiSeq™ 2500测序系统进行大鼠NAc的miRNA谱分析。结果CPP实验显示，METH可显著延长大鼠在药盒中的停留时间（从307 ± 97 s延长至592 ± 96 s）。病理学染色显示，MET组大鼠轴突扭曲，极化神经元减少。我们进一步鉴定了40种差异miRNA（17种上调和23种下调）和3种新型miRNA（新型237，296和501），它们对METH有反应。对差异miRNA潜在靶点的生物信息学分析表明，下游集中在Wnt信号通路、结核病、弓形虫病、剪接体、溶酶体和轴突导向。讨论和结论在大鼠NAc中鉴定了许多对METH应答的miRNA。这些METH调控的miRNAs为揭示METH成瘾的分子机制提供了新的视角。
Abstract Context MicroRNA (miRNA) is an important regulator of gene expression. Methamphetamine (METH) induces a variety of alterations in different systems by affecting gene expression, but the effects of METH on miRNA profiles need to be elucidated. Objectives This study develops a rat model of METH addiction, and analyzes the expression profile alterations of miRNA in nucleus accumbens (NAc) of the METH-addicted rats. Materials and methods Sprague-Dawley rats were administered 10 mg/kg METH or vehicle twice a day for 4 weeks. The addictive behaviour of rats was estimated by CPP test. The pathological changes of brain tissues were then observed by HE and Glee silver staining. The miRNA profile analysis of the NAc of the rats was performed using an Illumina HiSeq™ 2500 sequencing system. Results CPP test indicated that METH significantly prolonged the residence time of the rats in the drug box (from 307 ± 97 to 592 ± 96 s). The pathological staining showed the distorted axons, and fewer polarized neurons in the METH-treated rats. We further identified 40 differential miRNAs (17 up- and 23 down-regulated) and three novel miRNAs (novel 237, 296 and 501) that responded to METH. The bioinformatic analysis for the potential targets of the differential miRNA suggests that the downstream were concentrated in the Wnt signalling pathway, tuberculosis, toxoplasmosis, spliceosome, lysosome, and axon guidance. Discussion and conclusions A number of miRNAs responding to METH were identified in the NAc of rats. These METH-regulated miRNAs provide a new perspective for revealing the molecular mechanisms of METH addiction.
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DOI：
10.1523/jneurosci.2419-10.2010
发表时间：
2010-07-28
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
He Y;Yang C;Kirkmire CM;Wang ZJ
通讯作者：
Wang ZJ
影响因子：
64.5
作者：
Ashraf, SI;McLoon, AL;Kunes, S
通讯作者：
Kunes, S
影响因子：
10.6
作者：
Huang, Weihua;Li, Ming D.
通讯作者：
Li, Ming D.
影响因子：
7
作者：
Nensa, Fabian M.;Neumann, Martin H. D.;Mueller, Thorsten
通讯作者：
Mueller, Thorsten
影响因子：
3.7
作者：
Berry S;Weinmann O;Fritz AK;Rust R;Wolfer D;Schwab ME;Gerber U;Ster J
通讯作者：
Ster J