Methamphetamine-induced region-specific transcriptomic and epigenetic changes in the brain of male rats.
Methamphetamine-induced region-specific transcriptomic and epigenetic changes in the brain of male rats.
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DOI：
10.1038/s42003-023-05355-3
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发表时间：
2023-09-27
影响因子：
5.9
通讯作者：
Zhang, Bo
中科院分区：
文献类型：
--
作者：
Miao, Benpeng;Xing, Xiaoyun;Bazylianska, Viktoriia;Madden, Pamela;Moszczynska, Anna;Zhang, Bo
精神兴奋剂甲基苯丙胺（METH）对大脑有神经毒性，因此，滥用它会导致神经和精神疾病。基因调控网络（GRN）对神经毒性METH狂欢的反应在大多数大脑区域仍然不清楚。在这里，我们研究了在雄性大鼠的脑桥核，齿状回，阿蒙的角，和脑室下区的GRN狂欢METH的影响。在METH后24小时，约16%的基因显示出表达改变，超过四分之一的先前开放的染色质区域-基因通常活跃的基因组部分-显示出其可及性的变化。有趣的是，大多数变化是独特的每个研究领域，并观察到转录组和染色质可及性之间的独立调节。出乎意料的是，METH差异影响齿状回和阿蒙角内的基因活性和染色质可及性。大约70%的大鼠大脑中受影响的染色质可接近区域具有人类基因组中保守的DNA序列。这些区域经常充当增强子，提高附近基因的活性，并包含与各种神经系统疾病相关的突变。通过勾勒出与特定大脑区域中的METH狂欢相关的基因调控网络，我们的研究为METH如何引发深刻的区域特异性分子变化提供了新的见解。多组学分析揭示了急性外周甲基苯丙胺暴露对成年雄性大鼠奖励相关脑区的转录组学和表观基因组学影响。
Psychostimulant methamphetamine (METH) is neurotoxic to the brain and, therefore, its misuse leads to neurological and psychiatric disorders. The gene regulatory network (GRN) response to neurotoxic METH binge remains unclear in most brain regions. Here we examined the effects of binge METH on the GRN in the nucleus accumbens, dentate gyrus, Ammon’s horn, and subventricular zone in male rats. At 24 h after METH, ~16% of genes displayed altered expression and over a quarter of previously open chromatin regions - parts of the genome where genes are typically active - showed shifts in their accessibility. Intriguingly, most changes were unique to each area studied, and independent regulation between transcriptome and chromatin accessibility was observed. Unexpectedly, METH differentially impacted gene activity and chromatin accessibility within the dentate gyrus and Ammon’s horn. Around 70% of the affected chromatin-accessible regions in the rat brain have conserved DNA sequences in the human genome. These regions frequently act as enhancers, ramping up the activity of nearby genes, and contain mutations linked to various neurological conditions. By sketching out the gene regulatory networks associated with binge METH in specific brain regions, our study offers fresh insights into how METH can trigger profound, region-specific molecular shifts. A multi-omic analysis unveils the transcriptomic and epigenomic impact of acute, peripheral methamphetamine exposure on reward-related brain regions in adult, male rats.
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影响因子：
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14.9
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2.6
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