Research Paper Volume 12, Issue 15 pp 15446—15461
The spleen mediates chronic sleep restriction-mediated enhancement of LPS-induced neuroinflammation, cognitive deficits, and anxiety-like behavior
- 1 Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- 2 Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
Received: April 17, 2020 Accepted: June 22, 2020 Published: August 3, 2020https://doi.org/10.18632/aging.103659
How to Cite
Copyright © 2020 Xu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Chronic sleep restriction promotes neuroinflammation and cognitive deficits in neurodegenerative and neurobehavioral diseases. The spleens of mice exposed to chronic and repeated psychological stress serve as a reservoir of inflammatory myeloid cells that are released into the blood and brain following secondary acute stress. Here, we tested whether chronic and repeated short-term sleep restriction (CRSR) would exacerbate lipopolysaccharide (LPS)-induced neuroinflammation, cognitive deficits, and anxiety-like behavior in a spleen-dependent manner. LPS was administered to aged mice 14 days after exposure to CRSR consisting of three cycles of 7 days of sleep restriction with 7-day intervals in between. CRSR increased plasma proinflammatory cytokine levels, blood-brain barrier permeability, hippocampal proinflammatory cytokine levels, and transition of microglia to the M1 phenotype 24 h after LPS treatment. This in turn led to cognitive deficits and anxiety-like behavior. Interestingly, removal of the spleen 14 days prior to CRSR abrogated the enhancement of LPS-induced increases in systemic inflammation, neuroinflammation, cognitive deficits, and anxiety-like behavior. These data indicate that the spleen was essential for CRSR-induced exacerbation of LPS-induced brain damage.