在精神分裂症患者的额叶皮层中,抗精神病药物诱导的表观基因组重组
Bohan Zhu1, Richard I Ainsworth2, Zengmiao Wang2
1Department of Chemical Engineering, Virginia Tech, Blacksburg, United States.
eLife
|April 22, 2024
概括
大脑的表观遗传变化与精神分裂症风险有关,抗精神病药物和年龄影响这些标记. 这项研究揭示了精神分裂症患者的细胞特异性表观遗传差异,其中一些因治疗而逆转.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 是一个遗传学.
- 精神病学是一个精神病学.
背景情况:
- 全基因组关联研究确定精神分裂症风险位置,但仅仅遗传因素不能完全解释这种情况.
- 表观遗传修饰,就像基因组标记一样,是塑性的,受到环境因素的影响,包括抗精神病药物.
- 关于从精神分裂症患者获得的死后脑样本中的细胞特异性基因素修饰以及抗精神病治疗的影响的研究有限.
研究的目的:
- 为了研究细胞特异性全基因组基因组修饰 (H3K27ac,H3K4me3) 和基因表达 (RNA-seq) 在精神分裂症患者的前皮层.
- 为了比较无抗精神病药物 (AF) 和抗精神病药物 (AT) 治疗的精神分裂症患者和匹配的对照组之间的表观遗传学和转录基因特征.
- 确定抗精神病治疗和年龄对精神分裂症表观遗传景观的影响.
主要方法:
- 对H3K27ac (活性增强剂) 和H3K4me3 (活性促进剂) 的ChIP-seq分析.
- 用于基因表达特征的RNA测序 (RNA-seq).
- 分析了58个个人的死后额叶皮质样本 (精神分裂症AF,精神分裂症AT和对照).
主要成果:
- 在精神分裂症患者中观察到数千个神经元和非神经元表观遗传差异在关键风险位置 (例如NRG1,DISC1,DRD3).
- 鉴定了与精神分裂症相关的转录因子,其标和表观基因组/转录基因组特征的改变,其中一些因抗精神病治疗而逆转.
- 抗精神病治疗效应与精神分裂症特有的表观遗传变化有所区分. 年龄对AT精神分裂症患者的表观基因组景观有更明显的影响.
结论:
- 在精神分裂症患者的前额叶皮层中存在显著的表观遗传变化.
- 抗精神病治疗可以逆转与精神分裂症相关的某些表观遗传和转录基因变化.
- 这项研究强调了遗传学,表观遗传学,年龄和抗精神病药物在精神分裂症病理生理学的复杂相互作用.
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