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在对甲基苯丙胺表现出更易受影响反应的基因敲除小鼠纹状体中的基因表达谱分析

Gene Expression Profiling in the Striatum of KO Mice Exhibiting More Vulnerable Responses against Methamphetamine.

作者信息

Kim Mikyung, Jeon Se Jin, Custodio Raly James, Lee Hyun Jun, Sayson Leandro Val, Ortiz Darlene Mae D, Cheong Jae Hoon, Kim Hee Jin

机构信息

Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University, Seoul 01795, Republic of Korea.

Department of Chemistry Life Science, Sahmyook University, Seoul 01795, Republic of Korea.

出版信息

Biomol Ther (Seoul). 2021 Mar 1;29(2):135-143. doi: 10.4062/biomolther.2020.123.

DOI:10.4062/biomolther.2020.123
PMID:33342769
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7921858/
Abstract

Drug addiction influences most communities directly or indirectly. Increasing studies have reported the relationship between circadian-related genes and drug addiction. disrupted mice exhibited more vulnerable behavioral responses against some drugs including methamphetamine (METH). However, its roles and mechanisms are still not clear. Transcriptional profiling analysis in knockout (KO) mice may provide a valuable tool to identify potential genetic involvement and pathways in enhanced behavioral responses against drugs. To explore the potential genetic involvement, we examined common differentially expressed genes (DEGs) in the striatum of drug naïve KO/wild-type (WT) mice, and before/after METH treatment in KO mice, but not in WT mice. We selected 9 common DEGs (, , , , , , , , and ) based on literature research. Among the common DEGs, , , , and showed higher expression levels in drug naïve KO mice than in WT mice, while they were downregulated in KO mice after METH treatment. In contrast, , , , , and exhibited lower expression levels in drug naïve KO mice than in WT mice, while they were upregulated after METH treatment in KO mice. qRT-PCR analyses validated the expression patterns of 9 target genes before/after METH treatment in KO and WT mice. Although further research is required to deeply understand the relationship and roles of the 9 target genes in drug addiction, the findings from the present study indicate that the target genes might play important roles in drug addiction.

摘要

药物成瘾直接或间接地影响着大多数社区。越来越多的研究报道了昼夜节律相关基因与药物成瘾之间的关系。生物钟紊乱的小鼠对包括甲基苯丙胺(METH)在内的某些药物表现出更易受影响的行为反应。然而,其作用和机制仍不清楚。对基因敲除(KO)小鼠进行转录谱分析可能为识别增强的药物行为反应中潜在的基因参与和途径提供一个有价值的工具。为了探索潜在的基因参与情况,我们检测了未接触过药物的KO/野生型(WT)小鼠纹状体中,以及KO小鼠在METH处理前后(但WT小鼠未进行METH处理)的常见差异表达基因(DEG)。我们基于文献研究选择了9个常见的DEG(、、、、、、、、和)。在这些常见的DEG中,、、、和在未接触过药物的KO小鼠中的表达水平高于WT小鼠,而在METH处理后的KO小鼠中它们被下调。相反,、、、、和在未接触过药物的KO小鼠中的表达水平低于WT小鼠,而在KO小鼠经METH处理后它们被上调。qRT-PCR分析验证了KO和WT小鼠在METH处理前后9个靶基因的表达模式。尽管需要进一步研究来深入了解这9个靶基因在药物成瘾中的关系和作用,但本研究的结果表明这些靶基因可能在药物成瘾中起重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e0a/7921858/380777b7d7ca/bt-29-2-135-f8.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e0a/7921858/380777b7d7ca/bt-29-2-135-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e0a/7921858/366456bf01a0/bt-29-2-135-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e0a/7921858/c242f39af245/bt-29-2-135-f2.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e0a/7921858/c0535dffe12e/bt-29-2-135-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e0a/7921858/06b3bcf2f5f6/bt-29-2-135-f6.jpg
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