Huang Chia-Hung, Hsu Cho-Hsien, Tseng Bo-Yuan, Chang Man-Chen, Lai Yung-Chun, Lin Chun-Yen, Hsiao Chuhsing Kate, Lu Tzu-Pin, Yu Sung-Liang, Hsieh Sung-Tsang, Chen Wei J
Forensic Biology Division, Institute of Forensic Medicine, Ministry of Justice, New Taipei, Taiwan.
Forensic Pathology Division, Institute of Forensic Medicine, Ministry of Justice, New Taipei, Taiwan.
Neuropathol Appl Neurobiol. 2025 Oct;51(5):e70035. doi: 10.1111/nan.70035.
Despite the critical role of mitochondria in confronting alcohol challenges and providing energy, to date, there are no studies describing the effect of alcohol on mitochondrial epigenetics in energy-craving brain tissues. Focusing on the human nucleus accumbens (NAcc) and prefrontal cortex (PFC), we aimed to examine the effect of alcohol on mitochondrial DNA methylation.
We collected 105 brain tissue samples from 53 deceased individuals, classified into no antemortem alcohol use (n = 34), alcohol-ingested (n = 9) and alcohol-fermented (n = 10). Using whole-genome bisulphite sequencing, we constructed an alcohol intake (ALC) index summing the effect of differentially methylated cytosine sites between individuals with alcohol-ingested and individuals without antemortem alcohol use.
Compared to the group of alcohol-ingested, lower ALC index scores in both the NAcc and the PFC were found not only in the group of no antemortem alcohol use (p = 7.70 × 10 in the NAcc; 1.03 × 10 in the PFC) but also in the group of alcohol-fermented (p = 5.67 × 10 in the NAcc; 5.49 × 10 in the PFC). The findings of the differentially methylated cytosines and the performance of the ALC index were supported by permutation tests. In addition, we found that the individuals with an alcohol consumption history had higher ALC index scores in the NAcc (p = 0.044) but not in the PFC compared to those without an alcohol consumption history.
This study revealed the immediate and cumulative effects of alcohol on the mitochondrial epigenetics of the human brain and provided evidence to determine antemortem alcohol use.
尽管线粒体在应对酒精挑战和提供能量方面发挥着关键作用，但迄今为止，尚无研究描述酒精对能量需求旺盛的脑组织中线粒体表观遗传学的影响。以人类伏隔核（NAcc）和前额叶皮质（PFC）为研究对象，我们旨在研究酒精对线粒体DNA甲基化的影响。
我们从53名死者身上收集了105份脑组织样本，分为生前未饮酒组（n = 34）、饮酒组（n = 9）和酒精发酵组（n = 10）。使用全基因组亚硫酸氢盐测序，我们构建了一个酒精摄入量（ALC）指数，该指数综合了饮酒者和生前未饮酒者之间差异甲基化胞嘧啶位点的影响。
与饮酒组相比，不仅在生前未饮酒组中发现NAcc和PFC的ALC指数得分较低（NAcc中p = 7.70×10；PFC中p = 1.03×10），在酒精发酵组中也较低（NAcc中p = 5.67×10；PFC中p = 5.49×10）。差异甲基化胞嘧啶的研究结果和ALC指数的表现得到了置换检验的支持。此外，我们发现有饮酒史的个体在NAcc中的ALC指数得分高于无饮酒史的个体（p = 0.044），但在PFC中并非如此。
本研究揭示了酒精对人类大脑线粒体表观遗传学的即时和累积影响，并为确定生前饮酒情况提供了证据。
