Sleep drives metabolite clearance from the adult brain.

Xie L, Kang H, Xu Q, Chen MJ, Liao Y, Thiyagarajan M, O'Donnell J, Christensen DJ, Nicholson C, Iliff JJ

Science 2013

1. Science. 2013 Oct 18;342(6156):373-7. doi: 10.1126/science.1241224. Sleep drives metabolite clearance from the adult brain. Xie L(1), Kang H, Xu Q, Chen MJ, Liao Y, Thiyagarajan M, O'Donnell J, Christensen DJ, Nicholson C, Iliff JJ, Takano T, Deane R, Nedergaard M. Author information: (1)Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, NY 14642, USA. Comment in Science. 2013 Oct 18;342(6156):301. doi: 10.1126/science.342.6156.301. Science. 2013 Oct 18;342(6156):316-7. doi: 10.1126/science.1245798. Nat Rev Neurosci. 2013 Dec;14(12):816-7. doi: 10.1038/nrn3632. Nat Rev Neurol. 2013 Dec;9(12):657. doi: 10.1038/nrneurol.2013.230. Mov Disord. 2014 Jan;29(1):33. doi: 10.1002/mds.25765. Neurosurgery. 2014 Feb;74(2):N17-8. doi: 10.1227/01.neu.0000442978.07078.e5. 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. DOI: 10.1126/science.1241224 PMCID: PMC3880190 PMID: 24136970 [Indexed for MEDLINE]

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