Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China; National Institute of Biological Sciences, Beijing, China.
National Institute of Biological Sciences, Beijing, China; College of Biological Sciences, China Agricultural University, Beijing, China.
Cell. 2023 Dec 7;186(25):5500-5516.e21. doi: 10.1016/j.cell.2023.10.025. Epub 2023 Nov 27.
Most animals require sleep, and sleep loss induces serious pathophysiological consequences, including death. Previous experimental approaches for investigating sleep impacts in mice have been unable to persistently deprive animals of both rapid eye movement sleep (REMS) and non-rapid eye movement sleep (NREMS). Here, we report a "curling prevention by water" paradigm wherein mice remain awake 96% of the time. After 4 days of exposure, mice exhibit severe inflammation, and approximately 80% die. Sleep deprivation increases levels of prostaglandin D (PGD) in the brain, and we found that elevated PGD efflux across the blood-brain-barrier-mediated by ATP-binding cassette subfamily C4 transporter-induces both accumulation of circulating neutrophils and a cytokine-storm-like syndrome. Experimental disruption of the PGD/DP1 axis dramatically reduced sleep-deprivation-induced inflammation. Thus, our study reveals that sleep-related changes in PGD in the central nervous system drive profound pathological consequences in the peripheral immune system.
大多数动物都需要睡眠，而睡眠缺失会导致严重的病理生理后果，包括死亡。以前研究小鼠睡眠影响的实验方法一直无法持续剥夺动物的快速眼动睡眠 (REMS) 和非快速眼动睡眠 (NREMS)。在这里，我们报告了一种“水卷曲预防”范式，其中小鼠保持清醒的时间占 96%。经过 4 天的暴露，小鼠表现出严重的炎症，大约 80%的小鼠死亡。睡眠剥夺会增加大脑中的前列腺素 D (PGD) 水平，我们发现，由 ATP 结合盒亚家族 C4 转运蛋白介导的血脑屏障中 PGD 的流出增加，会导致循环中性粒细胞的积累和细胞因子风暴样综合征。PGD/DP1 轴的实验破坏显著降低了睡眠剥夺引起的炎症。因此，我们的研究表明，中枢神经系统中与睡眠相关的 PGD 变化会导致外周免疫系统发生深刻的病理后果。
