长期暴露于葡萄糖皮质类药物会在人体神经发育过程中放大抑制性神经元细胞命运
Leander Dony1,2,3,4,5, Anthi C Krontira1, Lea Kaspar1,2
1Department Genes and Environment, Max Planck Institute of Psychiatry, 80804 Munich, Germany.
Science advances
|February 14, 2025
概括
产前暴露于葡萄皮质激素 (GCs) 改变了人类大脑的发育,影响了基因调节和细胞系. 这项研究揭示了像GC这样的环境因素如何与神经发育障碍的遗传风险相互作用.
科学领域:
- 神经科学是一个神经科学.
- 发展生物学 发展生物学
- 遗传学 遗传学 是一个
背景情况:
- 人类大脑发育障碍与神经和精神疾病有关.
- 遗传因素是已知的贡献者,但分子层面的环境影响需要进一步研究.
- 葡萄皮质体 (GCs) 是产前环境风险的关键媒介.
研究的目的:
- 为了研究暴露于葡萄糖皮质醇 (GC) 对人类神经器官的分子和细胞效应.
- 描述在神经分化过程中因慢性GC暴露而改变的转录反应和基因调控网络.
- 了解环境风险因素如何与神经发育中的遗传倾向融合.
主要方法:
- 使用单细胞和细胞类型特定的技术.
- 集成的单细胞转录学与染色体可访问性数据.
- 在分化过程中暴露于慢性GC暴露的未经指导的人类神经器官.
主要成果:
- 在暴露于GC后,确定了持续的,细胞类型特定的转录变化.
- 观察到自闭症风险基因和关键神经发育转录因子的改变.
- 证明GC暴露通过像PBX3.3这样的转录因子启动抑制性神经元系.
结论:
- 长期暴露于GC会导致神经器官发育的显著,持久的变化.
- 像GC这样的环境因素可以通过谱系规范的共享机制与遗传风险因素融合.
- 这项研究提供了关于产前环境暴露如何影响神经发育和疾病风险的分子见解.
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