Chronic sleep fragmentation impairs brain interstitial clearance in young wildtype mice

• Published in: Journal of cerebral blood flow and metabolism Vol. 44; no. 9; pp. 1515 - 1531
• Main Authors: Deng, Saiyue, Hu, Yusi, Chen, Simiao, Xue, Yang, Yao, Di, Sun, Qian, Nedergaard, Maiken, Wang, Wei, Ding, Fengfei
• Format: Journal Article
• Language: English
• Published: United States 01.09.2024
• Subjects: Animals; Brain - metabolism; Cognition - physiology; Glymphatic System - metabolism; Glymphatic System - physiopathology; Male; Mice; Mice, Inbred C57BL; Sleep Deprivation - metabolism; Sleep Deprivation - physiopathology; Sleep fragmentation; Interstitial clearance; Glymphatic function; Vasomotion; Pulsatility
• ISSN: 0271-678X; 1559-7016; 1559-7016
• DOI: 10.1177/0271678X241230188

Accumulating evidence shows that most chronic neurological diseases have a link with sleep disturbances, and that patients with chronically poor sleep undergo an accelerated cognitive decline. Indeed, a single-night of sleep deprivation may increase metabolic waste levels in cerebrospinal fluid. However, it remains unknown how chronic sleep disturbances in isolation from an underlying neurological disease may affect the glymphatic system. Clearance of brain interstitial waste by the glymphatic system occurs primarily during sleep, driven by multiple oscillators including arterial pulsatility, and vasomotion. Herein, we induced sleep fragmentation in young wildtype mice and assessed the effects on glymphatic activity and cognitive functions. Chronic sleep fragmentation reduced glymphatic function and impaired cognitive functions in healthy mice. A mechanistic analysis showed that the chronic sleep fragmentation suppressed slow vasomotion, without altering cardiac-driven pulsations. Taken together, results of this study document that chronic sleep fragmentation suppresses brain metabolite clearance and impairs cognition, even in the absence of disease.