1. Prolonged sleep deprivation induces a cytokine-storm-like syndrome in mammals.
- Author
-
Sang, Di, Lin, Keteng, Yang, Yini, Ran, Guangdi, Li, Bohan, Chen, Chen, Li, Qi, Ma, Yan, Lu, Lihui, Cui, Xi-Yang, Liu, Zhibo, Lv, Sheng-Qing, Luo, Minmin, Liu, Qinghua, Li, Yulong, and Zhang, Eric Erquan
- Subjects
- *
SLEEP deprivation , *RAPID eye movement sleep , *NON-REM sleep , *NEUTROPHILS , *CENTRAL nervous system - 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 D 2 (PGD 2) in the brain, and we found that elevated PGD 2 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 2 /DP1 axis dramatically reduced sleep-deprivation-induced inflammation. Thus, our study reveals that sleep-related changes in PGD 2 in the central nervous system drive profound pathological consequences in the peripheral immune system. [Display omitted] • A highly efficient paradigm is introduced for depriving mice of sleep • PGD 2 efflux across the BBB is enhanced by sleep deprivation • Sleep deprivation triggers increases in both cytokines and circulating neutrophils • The sleep-deprived brain affects the peripheral immune system via the PGD 2 /DP1 axis Enhanced efflux of PGD 2 across the BBB during prolonged sleep deprivation induces a cytokine-storm-like syndrome via the PGD 2 /DP1 axis. Sleep deprivation in mice that involves disruption of REMS and NREMS leads to lethality due to brain prostaglandin D 2 -mediated cytokine-storm-like systemic inflammation. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF