血脑屏障中的生理时钟调节了外来生物流动
Shirley L Zhang1, Zhifeng Yue2, Denice M Arnold2
1Center for Sleep and Circadian Neurobiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Chronobiology Program at Penn and Howard Hughes Medical Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Cell
|March 13, 2018
概括
循环节律会影响药物的有效性. 在果中, 血脑屏障在夜间更容易透,
科学领域:
- 神经科学
- 时间生物学
- 分子生物学
背景情况:
- 内生昼夜节律会影响生物体对外部因素的反应.
- 对于环境侮辱和治疗方法的日间时间差异背后的机制尚不清楚.
- 血脑屏障 (BBB) 在调节物质进入中枢神经系统方面起着至关重要的作用.
研究的目的:
- 调查昼夜节律在调节Drosophila血脑屏障 (BBB) 的作用.
- 阐明生物节律调节影响BBB透性和药物疗效的分子机制.
- 对中枢神经系统 (CNS) 疾病的日间药物使用的治疗影响进行探索.
主要方法:
- 使用Drosophila的异生物模型来评估BBB的透性.
- 研究了周围神经细胞中昼夜调节和分子钟组件的作用.
- 检查了间隙连接在质层之间的信号传输中的功能.
- 测量细胞内水平 ([Mg2+]i) 在下腺细胞 (SPG) 中.
- 在Drosophila发作模型中评估氨酸的疗效.
主要成果:
- 草BBB的透性表现出一个昼夜节律,在晚上更高.
- 循环调节的流量传送器,由周围神经中的分子时钟控制,驱动BBB透率节奏.
- 循环表达的间隙连接对于在BBB层中传输昼夜信号至关重要.
- 在SPG中细胞内 ([Mg2+]i) 的夜间降低与流量减少相关.
- 在Drosophila发作模型中,夜间服用素显示出更强的疗效.
结论:
- 通过质时钟控制流量,确定了影响BBB透性的生物节律调节的新机制.
- 证明BBB的透性和药物的有效性会随着时间的变化而变化.
- 突出了对中枢神经系统向药物的时间治疗潜力,建议优化药物给药时间.
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