细胞类型特异性表观遗传原始化基因表达在核中由可卡因
Philipp Mews1, Yentl Van der Zee1, Ashik Gurung1
1Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
长期暴露于可卡因会改变大脑的表观遗传学,在D1MSN中削减了组织蛋白变体H2A.Z. 这种表观遗传变化使大脑为复发做好了准备,突出显示了基因组变体交换作为关键的成机制.
科学领域:
- 神经科学是一个神经科学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
背景情况:
- 成的特点是复发,即使经过长时间的戒断期.
- 核 (NAc) 对于激励和药物奖励至关重要.
- 表观遗传修饰在成和复发中起作用.
研究的目的:
- 研究可卡因诱导的复发背后的表观遗传机制.
- 为了确定特定的组织组织蛋白修饰及其在NAc中的作用.
主要方法:
- 动物模型中的慢性可卡因暴露.
- 在NAc.中进行染色体分析和基因表达分析.
- 在D1MSN中选择性淘汰基因素伴侣ANP32E.
主要成果:
- 可卡因戒断在D1MSN中削弱了基因组变异H2A.Z,增加了基因组的可访问性.
- 这种枯竭启动了基因转录,导致在复发时异常的基因表达.
- 击败ANP32E阻止了H2A.Z的耗尽,并阻止了可卡因的奖励作用.
- D2 MSN 对可卡因暴露,戒断和复发有不同的反应.
结论:
- 基因组变异交换是滥用药物利用的关键表观遗传机制.
- 通过ANP32E介导的H2A.Z去除对于可卡因的奖励效果和复发至关重要.
- 向激素变体交换提供了一个潜在的成治疗策略.
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