GABA B1 受体中的胞嘧啶甲基化鉴定了男性血液和脑组织中与酒精相关的变化。
Cytosine methylation in GABA B1 receptor identifies alcohol-related changes for men in blood and brain tissues.
机构信息
Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Carl- Neuberg Str. 1, 30625 Hannover, Germany.
Institute of Legal Medicine, Hannover Medical School, Carl-Neuberg Str. 1, 30625 Hannover, Germany.
出版信息
Alcohol Alcohol. 2023 May 9;58(3):308-314. doi: 10.1093/alcalc/agad022.
AIMS
Alcohol use alters the reward signaling processes contributing to the development of addiction. We studied the effects of alcohol use disorder (AUD) on brain regions and blood of deceased women and men to examine sex-dependent differences in epigenetic changes associated with AUD. We investigated the effects of alcohol use on the gene promoter methylation of GABBR1 coding for GABAB receptor subunit 1 in blood and brain.
METHODS
We chose six brain regions associated with addiction and the reward pathway (nucleus arcuatus, nucleus accumbens, the mamillary bodies, amygdala, hippocampus and anterior temporal cortex) and performed epigenetic profiling of the proximal promoter of the GABBR1 gene of post-mortem brain and blood samples of 17 individuals with AUD pathology (4 female, 13 male) and 31 healthy controls (10 female, 21 male).
RESULTS
Our results show sex-specific effects of AUD on GABBR1 promoter methylation. Especially, CpG -4 showed significant tissue-independent changes and significantly decreased methylation levels for the AUD group in the amygdala and the mammillary bodies of men. We saw prominent and consistent change in CpG-4 across all investigated tissues. For women, no significant loci were observed.
CONCLUSION
We found sex-dependent differences in GABBR1 promoter methylation in relation to AUD. CpG-4 hypomethylation in male individuals with AUD is consistent for most brain regions. Blood shows similar results without reaching significance, potentially serving as a peripheral marker for addiction-associated neuronal adaptations. Further research is needed to discover more contributing factors in the pathological alterations of alcohol addiction to offer sex-specific biomarkers and treatment.
目的
饮酒改变了导致成瘾发展的奖励信号过程。我们研究了酒精使用障碍（AUD）对女性和男性已故者大脑区域和血液的影响，以检查与 AUD 相关的表观遗传变化中的性别依赖性差异。我们研究了饮酒对血液和大脑中 GABAB 受体亚单位 1 编码基因 GABBR1 启动子甲基化的影响。
方法
我们选择了与成瘾和奖励途径相关的六个大脑区域（弓状核、伏隔核、乳头体、杏仁核、海马体和前颞叶皮质），并对 17 名 AUD 患者（4 名女性，13 名男性）和 31 名健康对照者（10 名女性，21 名男性）的死后大脑和血液样本中的 GABBR1 基因近端启动子进行了表观遗传分析。
结果
我们的结果显示 AUD 对 GABBR1 启动子甲基化具有性别特异性影响。特别是，CpG-4 在男性的杏仁核和乳头体中表现出与 AUD 组显著的组织独立变化，并且甲基化水平显著降低。我们在所有研究的组织中都看到了 CpG-4 的明显且一致的变化。对于女性，没有观察到显著的基因座。
结论
我们发现与 AUD 相关的 GABBR1 启动子甲基化存在性别依赖性差异。AUD 男性个体的 CpG-4 低甲基化在大多数大脑区域都是一致的。血液显示出类似的结果，但没有达到显著性，可能是成瘾相关神经元适应的外周标志物。需要进一步研究以发现更多与酒精成瘾的病理性改变有关的因素，以提供针对特定性别的生物标志物和治疗方法。
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