The effect of morphine upon DNA methylation in ten regions of the rat brain

The effect of morphine upon DNA methylation in ten regions of the rat brain
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吗啡对大鼠大脑十个区域 DNA 甲基化的影响。

DOI:
10.1080/15592294.2017.1398296
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发表时间:
2017-01-01
期刊:
影响因子:
3.7
通讯作者:
Guo, Liqiong
Guo, Liqiong
中科院分区:
生物学3区
文献类型:
--
作者:
Barrow, Timothy M.;Byun, Hyang-Min;Guo, Liqiong

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吗啡是医学上最有效的镇痛剂之一。然而,它的使用与耐受性和依赖性的发展有关。最近的研究表明,在接触阿片类药物后,大脑中的表观遗传学变化为可能的成瘾机制提供了洞察。在这项研究中,我们试图确定急性和慢性吗啡暴露后大鼠大脑十个区域的表观遗传学变化。我们分析了与脑功能有关的六个核编码基因(BDNF、COMT、IL1b、IL6、NR3C1和TNF)和三个线粒体编码基因(Mtco1、MtCO2和Mtco3)的DNA甲基化,并测量了全球5-甲基胞嘧啶(5mC)和5-羟甲基胞嘧啶(5hmC)水平。我们观察到急性吗啡暴露后,脑桥BDNF和IL6、小脑NR3c1和海马区IL1b的甲基化程度不同(均P<0.05)。慢性暴露与脑桥BDNF和COMT、海马区NR3C1区和延髓IL1b区不同甲基化水平相关(均P
Morphine is one of the most effective analgesics in medicine. However, its use is associated with the development of tolerance and dependence. Recent studies demonstrating epigenetic changes in the brain after exposure to opiates have provided insight into mechanisms possibly underlying addiction. In this study, we sought to identify epigenetic changes in ten regions of the rat brain following acute and chronic morphine exposure. We analyzed DNA methylation of six nuclear-encoded genes implicated in brain function (Bdnf, Comt, Il1b, Il6, Nr3c1, and Tnf) and three mitochondrially-encoded genes (Mtco1, Mtco2, and Mtco3), and measured global 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) levels. We observed differential methylation of Bdnf and Il6 in the pons, Nr3c1 in the cerebellum, and Il1b in the hippocampus in response to acute morphine exposure (all P value < 0.05). Chronic exposure was associated with differential methylation of Bdnf and Comt in the pons, Nr3c1 in the hippocampus and Il1b in the medulla oblongata (all P value