在大脑微血管系统中对昼夜节律的药理学调节
Zhenglang Yang1, Mari Kim1, Meera Montgomery1
1Cell Biology Department, Emory University, Atlanta, GA, USA.
概括
血脑屏障是血液与大脑之间的屏障.
科学领域:
- 神经科学是一个神经科学.
- 时间生物学 时间生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 血脑屏障 (BBB) 保护大脑,其功能受到昼夜节律的影响.
- BBB中的内皮细胞钟会影响药物清除,但药理控制尚未研究.
研究的目的:
- 为了研究血脑屏障的昼夜动态.
- 为了探索BBB时钟的药理学调制.
主要方法:
- 隔离的小鼠大脑微血管 (MVs) 与PER2::iLuc记者系统一起用于监测ex vivo昼夜节律.
- 用小分子昼夜调节器治疗了MV和人类微血管细胞系.
- 在调节器给药后,在小鼠中评估了药物排放节奏.
主要成果:
- 辛森塞丁和KL001在体外调节了BBB昼夜节律.
- 在体内,KL001和sinensetin改变了昼夜基因表达和BBB排泄节奏.
- 在孤立的微容器中,循环节律被维持在活体中.
结论:
- 血脑屏障昼夜节律在药理上是可以处理的.
- 小分子调节器有潜力通过慢药学优化中枢神经系统的药物输送.
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