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青少年压力诱导的多巴胺基神经元通过葡萄糖皮质类药物进行表观遗传控制
Minae Niwa1, Hanna Jaaro-Peled, Stephanie Tankou
1Department of Chemical Pharmacology, Meijo University Graduate School of Pharmaceutical Sciences, Nagoya, Japan.
概括
青少年的压力和遗传风险可以引发大脑的表观遗传变化,导致成人神经精神疾病,如精神病性抑郁症. 葡萄糖皮质类药物调解这种联系,影响多巴胺神经元功能.
科学领域:
- 神经科学是一个神经科学.
- 分子精神病学分子精神病学
- 发展心理学 发展心理学
背景情况:
- 儿童和青少年的环境压力因素会影响大脑发育和成人行为.
- 过度的压力可能导致成人发病的神经精神疾病.
- 葡萄糖皮质类药物涉及将压力与表观遗传变化联系起来.
研究的目的:
- 阐明由葡萄糖皮质体介导的青少年压力因素影响神经元内表观遗传控制的机制.
- 研究多巴胺系统中压力,遗传和表观遗传修饰之间的联系.
- 用小鼠模型建模精神病性抑郁症.
主要方法:
- 使用了一只被轻度隔离压力的小鼠模型.
- 检查了表观遗传修饰,特别是多巴胺神经元中氨酸氧化酶基因的DNA高甲基化.
- 评估了神经化学和行为缺陷.
- 使用一种葡萄糖皮质醇受体抗剂.
主要成果:
- 轻微的隔离压力,结合遗传风险,诱导了中皮层多巴胺基神经元中铁酸酶基因的DNA高甲基化.
- 这些分子变化与神经化学和行为缺陷相关.
- 观察到的缺陷和分子变化被一种葡萄糖皮质体受体对抗剂逆转.
结论:
- 葡萄糖皮质类药物在将青少年的压力与多巴胺基神经元的表观遗传变化联系起来方面发挥着至关重要的作用.
- 这种机制涉及压力,糖皮质类药物和表观遗传学,有助于神经精神疾病的发展,如精神病性抑郁症.
- 鼠标模型有效地复制了精神病抑郁症的关键生物和表型方面.
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