Early life stress and voluntary alcohol consumption in relation to Maoa methylation in male rats
Early life stress and voluntary alcohol consumption in relation to Maoa methylation in male rats
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DOI：
10.1016/j.alcohol.2018.11.001
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发表时间：
2019-09-01
期刊：
影响因子：
2.3
通讯作者：
Comasco, Erika
中科院分区：
文献类型：
--
作者：
Bendre, Megha;Granholm, Linnea;Comasco, Erika
早期生活压力（ELS）或饮酒会影响DNA甲基化并影响基因表达。单胺氧化酶A（Maoa）编码代谢单胺能神经递质的酶，这些神经递质对应激反应、酒精奖励和强化至关重要。以前，我们报道了较低的Maoa表达的雄性大鼠的延髓核和背侧纹状体暴露于ELS在出生后的前三周，并自愿饮酒在成年期，与对照组相比。本研究继续研究ELS和饮酒对Maoa甲基化的影响，以及其与这些动物中Maoa表达的关系。我们在一个大鼠亚组中对Maoa启动子、内含子1-5以及外显子5和6进行下一代亚硫酸氢盐测序后选择了候选CpG，这些CpG共同由107个CpG（5 '-胞嘧啶-磷酸-鸟苷-3'）组成。焦磷酸测序用于分析整个样品中启动子和内含子1中10个候选CpG的甲基化。ELS和酒精对背侧纹状体中CpG特异性甲基化表现出交互作用。CpG特异性甲基化与Maoa表达、皮质酮水平和酒精消耗以脑区域特异性方式相关。Maoa启动子中CpG特异性甲基化是ELS与饮酒对NAc中Maoa表达的相互作用的潜在调节剂。然而，这些发现是稀疏的，没有经过多次测试的校正，甲基化水平的差异幅度很小。总之，启动子和内含子1中的CpG特异性Maoa甲基化可能与ELS、饮酒和奖励相关脑区域中的Maoa表达相关。(C)2018爱思唯尔公司All rights reserved.
Early life stress (ELS) or alcohol consumption can influence DNA methylation and affect gene expression. Monoamine oxidase A (Maoa) encodes the enzyme that metabolizes monoaminergic neurotransmitters crucial for the stress response, alcohol reward, and reinforcement. Previously, we reported lower Maoa expression in the nucleus accumbens and dorsal striatum of male rats exposed to ELS during the first three postnatal weeks, and to voluntary alcohol consumption in adulthood, compared with controls. The present study continued to investigate the effect of ELS and alcohol consumption on Maoa methylation, and its relation to Maoa expression in these animals. We selected candidate CpGs after performing next generation bisulfite sequencing of the Maoa promoter, intron 1-5, and exons 5 and 6, together composed of 107 CpGs (5'-cytosine-phosphate-guanosine-3'), in a subgroup of rats. Pyrosequencing was used to analyze the methylation of 10 candidate CpGs in the promoter and intron 1 in the entire sample. ELS and alcohol displayed an interactive effect on CpG-specific methylation in the dorsal striatum. CpG-specific methylation correlated with Maoa expression, corticosterone levels, and alcohol consumption in a brain region-specific manner. CpG-specific methylation in the Maoa promoter was a potential moderator of the interaction of ELS with alcohol consumption on Maoa expression in the NAc. However, the findings were sparse, did not survive correction for multiple testing, and the magnitude of differences in methylation levels was small. In conclusion, CpG-specific Maoa methylation in the promoter and intron 1 may associate with ELS, alcohol consumption, and Maoa expression in reward-related brain regions. (C) 2018 Elsevier Inc. All rights reserved.