Neurobiology of Behaviour Research Group (GReNeC-NeuroBio), Universitat Pompeu Fabra (UPF), Barcelona, Spain.
Molecular and Cellular Pathology of Alcohol, Prince Felipe Research Centre, Valencia, Spain.
J Psychopharmacol. 2019 Dec;33(12):1562-1572. doi: 10.1177/0269881119856001. Epub 2019 Jun 18.
Alcohol exposure impairs brain development and leads to a range of behavioural and cognitive dysfunctions, termed as foetal alcohol spectrum disorders. Although different mechanisms have been proposed to participate in foetal alcohol spectrum disorders, the molecular insights of such effects are still uncertain. Using a mouse model of foetal alcohol spectrum disorder, we have previously shown that maternal binge-like alcohol drinking causes persistent effects on motor, cognitive and emotional-related behaviours associated with neuroimmune dysfunctions.
In this study, we sought to evaluate whether the long-term behavioural alterations found in offspring with early exposure to alcohol are associated with epigenetic changes in the hippocampus and prefrontal cortex.
Pregnant C57BL/6 female mice underwent a model procedure for binge alcohol drinking throughout both the gestation and lactation periods. Subsequently, adult offspring were assessed for their cognitive function in a reversal learning task and brain areas were extracted for epigenetic analyses.
The results demonstrated that early binge alcohol exposure induces long-term behavioural effects along with alterations in histone acetylation (histone H4 lysine 5 and histone H4 lysine 12) in the hippocampus and prefrontal cortex. The epigenetic effects were linked with an imbalance in histone acetyltransferase activity that was found to be increased in the prefrontal cortex of mice exposed to alcohol.
In conclusion, our results reveal that maternal binge-like alcohol consumption induces persistent epigenetic modifications, effects that might be associated with the long-term cognitive and behavioural impairments observed in foetal alcohol spectrum disorder models.
酒精暴露会损害大脑发育，并导致一系列行为和认知功能障碍，即胎儿酒精谱系障碍。虽然已经提出了不同的机制来参与胎儿酒精谱系障碍，但这些影响的分子见解仍不确定。我们之前使用胎儿酒精谱系障碍的小鼠模型表明，母体 binge 样饮酒会导致与神经免疫功能障碍相关的运动、认知和情绪相关行为的持续影响。
在这项研究中，我们试图评估早期暴露于酒精的后代中发现的长期行为改变是否与海马体和前额叶皮层中的表观遗传变化有关。
怀孕的 C57BL/6 雌性小鼠在整个妊娠期和哺乳期都经历了 binge 酒精饮用的模型程序。随后，对成年后代进行反转学习任务的认知功能评估，并提取大脑区域进行表观遗传分析。
结果表明，早期 binge 酒精暴露会导致长期的行为效应，同时还会改变海马体和前额叶皮层中的组蛋白乙酰化（组蛋白 H4 赖氨酸 5 和组蛋白 H4 赖氨酸 12）。表观遗传效应与组蛋白乙酰转移酶活性的不平衡有关，在暴露于酒精的小鼠的前额叶皮层中发现这种活性增加。
总之，我们的结果表明，母体 binge 样饮酒会引起持续的表观遗传修饰，这些效应可能与胎儿酒精谱系障碍模型中观察到的长期认知和行为损伤有关。
