Abstract：
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 D2 (PGD2) in the brain, and we found that elevated PGD2 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 PGD2/DP1 axis dramatically reduced sleep-deprivation-induced inflammation. Thus, our study reveals that sleep-related changes in PGD2 in the central nervous system drive profound pathological consequences in the peripheral immune system.
摘要：
大多数动物需要睡眠，睡眠不足会导致严重的病理生理后果，包括死亡。以前用于研究小鼠睡眠影响的实验方法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）。这里,我们报告了一种“水预防卷曲”模式，其中小鼠96%的时间保持清醒。暴露4天后，小鼠表现出严重的炎症，大约80%的人死亡。睡眠不足会增加大脑中前列腺素D2（PGD2）的水平，我们发现，由ATP结合盒亚家族C4转运蛋白介导的PGD2跨血脑屏障的外排升高，可诱导循环中性粒细胞的积累和细胞因子风暴样综合征。PGD2/DP1轴的实验性破坏显著减少了睡眠剥夺诱导的炎症。因此，我们的研究表明,中枢神经系统中PGD2的睡眠相关变化在外周免疫系统中引起了深刻的病理后果.
