Behavioral sensitization induced by methamphetamine causes differential alterations in gene expression and histone acetylation of the prefrontal cortex in rats.
Behavioral sensitization induced by methamphetamine causes differential alterations in gene expression and histone acetylation of the prefrontal cortex in rats.
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DOI：
10.1186/s12868-021-00616-5
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发表时间：
2021-04-06
期刊：
影响因子：
2.4
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Li H;Chen JA;Ding QZ;Lu GY;Wu N;Su RB;Li F;Li J
甲基苯丙胺 (METH) 是全世界滥用最广泛的非法物质之一；不幸的是，其成瘾机制仍不清楚。根据越来越多的证据，基因表达和染色质修饰的变化可能与冰毒对大脑的持续影响有关。在本研究中，我们利用冰毒诱导的行为敏化作为反映药物成瘾某些方面的动物模型，并检查了成年大鼠前额皮质（PFC）基因表达和组蛋白乙酰化的变化。我们进行了 mRNA 微阵列和染色质免疫沉淀 (ChIP) 与 DNA 微阵列 (ChIP 芯片) 分析的结合，以筛选和识别转录水平和组蛋白乙酰化模式的变化。进行功能富集分析，包括基因本体论（GO）和京都基因和基因组百科全书（KEGG）分析，以分析差异表达的基因。然后，我们使用 qPCR 和 ChIP-PCR 检测进一步鉴定了 ANP32A（酸性富含亮氨酸核磷蛋白-32A）和 POU3F2（POU 结构域，3 类，转录因子 2）的变化。在冰毒诱导的行为敏化大鼠模型中，冰毒激发导致275个差异表达基因和许多基因高度乙酰化（821个基因具有H3乙酰化，10个基因具有H4乙酰化）。根据 mRNA 微阵列以及 GO 和 KEGG 富集分析，24 个基因可能参与 METH 诱导的行为敏化，其中 7 个基因通过 qPCR 得到确认。我们进一步检查了 METH 诱导的行为敏化不同时期 ANP32A 和 POU3F2 转录本和组蛋白乙酰化水平的变化。 H4 过度乙酰化导致 ANP32A mRNA 水平增加，H3/H4 过度乙酰化导致 POU3F2 mRNA 水平增加，这是由 METH 激发诱导的行为敏化引起的，但不是由急性 METH 暴露引起的。目前的结果揭示了 METH 暴露导致大鼠 PFC 转录和组蛋白乙酰化的改变，并提供了组蛋白乙酰化修饰导致 METH 诱导的行为敏化引起的基因表达改变的证据。
Methamphetamine (METH) is one of the most widely abused illicit substances worldwide; unfortunately, its addiction mechanism remains unclear. Based on accumulating evidence, changes in gene expression and chromatin modifications might be related to the persistent effects of METH on the brain. In the present study, we took advantage of METH-induced behavioral sensitization as an animal model that reflects some aspects of drug addiction and examined the changes in gene expression and histone acetylation in the prefrontal cortex (PFC) of adult rats. We conducted mRNA microarray and chromatin immunoprecipitation (ChIP) coupled to DNA microarray (ChIP-chip) analyses to screen and identify changes in transcript levels and histone acetylation patterns. Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, were performed to analyze the differentially expressed genes. We then further identified alterations in ANP32A (acidic leucine-rich nuclear phosphoprotein-32A) and POU3F2 (POU domain, class 3, transcription factor 2) using qPCR and ChIP-PCR assays. In the rat model of METH-induced behavioral sensitization, METH challenge caused 275 differentially expressed genes and a number of hyperacetylated genes (821 genes with H3 acetylation and 10 genes with H4 acetylation). Based on mRNA microarray and GO and KEGG enrichment analyses, 24 genes may be involved in METH-induced behavioral sensitization, and 7 genes were confirmed using qPCR. We further examined the alterations in the levels of the ANP32A and POU3F2 transcripts and histone acetylation at different periods of METH-induced behavioral sensitization. H4 hyperacetylation contributed to the increased levels of ANP32A mRNA and H3/H4 hyperacetylation contributed to the increased levels of POU3F2 mRNA induced by METH challenge-induced behavioral sensitization, but not by acute METH exposure. The present results revealed alterations in transcription and histone acetylation in the rat PFC by METH exposure and provided evidence that modifications of histone acetylation contributed to the alterations in gene expression caused by METH-induced behavioral sensitization.
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影响因子：
3.7
作者：
Martin TA;Jayanthi S;McCoy MT;Brannock C;Ladenheim B;Garrett T;Lehrmann E;Becker KG;Cadet JL
通讯作者：
Cadet JL
DOI：
10.1016/j.pnpbp.2018.07.019
发表时间：
2019-01-10
影响因子：
5.6
作者：
González B;Torres OV;Jayanthi S;Gomez N;Sosa MH;Bernardi A;Urbano FJ;García-Rill E;Cadet JL;Bisagno V
通讯作者：
Bisagno V
影响因子：
4.7
作者：
Nestler EJ
通讯作者：
Nestler EJ
影响因子：
4.8
作者：
Adegbola, O;Pasternack, GR
通讯作者：
Pasternack, GR
海马中雷帕霉素信号通路磷脂酰肌醇 3-激酶/Akt-哺乳动物靶点的激活对于大鼠获得吗啡诱导的位置偏好至关重要。
影响因子：
3.3
作者：
Cui, Yue;Zhang, X. Q.;Liu, X. G.
通讯作者：
Liu, X. G.