酒精新陈代谢有助于大脑基因素乙化
P Mews1,2, G Egervari3, R Nativio1
1Epigenetics Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Nature
|October 25, 2019
概括
酒精代谢直接影响大脑的基因调节. 酒精衍生的乙酸通过ACSS2促进基因素乙化,影响学习和记忆,以及与酒精相关的行为.
科学领域:
- 神经科学
- 表观遗传学
- 代谢过程
背景情况:
- 表观遗传调节,包括基因素乙化,受代谢状态的影响.
- 在神经元中对基因素乙化至关重要的乙-CoA由乙-CoA合成酶2 (ACSS2) 从乙酸中产生.
- 酒精代谢显著增加血中乙酸盐水平,这表明酒精消耗与神经元表观遗传修饰之间存在联系.
研究的目的:
- 调查酒精代谢是否直接影响大脑中的乙烯化.
- 确定乙-CoA合成酶2 (ACSS2) 在酒精诱导的表观遗传变化中的作用.
- 探索酒精衍生的乙酸对神经元基因表达和行为的影响.
主要方法:
- 在小鼠体内进行稳定同位素标记,以追踪乙基的起源.
- 用标注的酒精和酸盐来评估将其纳入大脑质素.
- 用初级海马神经元进行体外实验以研究转录反应.
- 在存在或不存在ACSS2活性的酒精相关联学习的体内评估.
主要成果:
- 酒精新陈代谢被证明会在大脑中引起快速的基因组乙化.
- 观察到由酒精衍生的乙基直接沉积到依赖ACSS2的基因组上.
- 标记的酸盐和酒精暴露导致胎儿大脑中的乙基结合.
- 对ACSS2抑制敏感的神经元的细胞外诱导学习和记忆相关的转录程序.
- 发现与酒精相关的关联学习需要ACSS2.
结论:
- 酒精代谢通过ACSS2依赖的途径直接促进大脑中的基因素乙化.
- 这种机制将酒精消费与大脑中的基因调节联系在一起,
- 这些发现突显出酒精,表观遗传修饰和学习和记忆等认知过程之间的直接代谢联系.
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