Sleep Drives Metabolite Clearance from the Adult Brain

Lulu Xie(University of Rochester Medical Center), Hongyi Kang(University of Rochester Medical Center), Qiwu Xu(University of Rochester Medical Center), Michael Chen(University of Rochester Medical Center), Yonghong Liao(University of Rochester Medical Center), Meenakshisundaram Thiyagarajan(University of Rochester Medical Center), John O’Donnell(University of Rochester Medical Center), Daniel J. Christensen(University of Rochester Medical Center), Charles Nicholson(NYU Langone Health), Jeffrey J. Iliff(University of Rochester Medical Center), Takahiro Takano(University of Rochester Medical Center), Rashid Deane(University of Rochester Medical Center), Maiken Nedergaard(University of Rochester Medical Center)
Science
October 17, 2013
Cited by 5,232Open Access
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Abstract

The conservation of sleep across all animal species suggests that sleep serves a vital function. We here report that sleep has a critical function in ensuring metabolic homeostasis. Using real-time assessments of tetramethylammonium diffusion and two-photon imaging in live mice, we show that natural sleep or anesthesia are associated with a 60% increase in the interstitial space, resulting in a striking increase in convective exchange of cerebrospinal fluid with interstitial fluid. In turn, convective fluxes of interstitial fluid increased the rate of β-amyloid clearance during sleep. Thus, the restorative function of sleep may be a consequence of the enhanced removal of potentially neurotoxic waste products that accumulate in the awake central nervous system.


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