title: Sleep drives metabolite clearance from the adult brain.
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.
authors.affiliation: Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, NY 14642, USA.
authors.forename: Lulu
authors.initials: L
authors.lastname: Xie
authors.forename: Hongyi
authors.initials: H
authors.lastname: Kang
authors.forename: Qiwu
authors.initials: Q
authors.lastname: Xu
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Chen
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Liao
authors.forename: Meenakshisundaram
authors.initials: M
authors.lastname: Thiyagarajan
authors.forename: John
authors.initials: J
authors.lastname: O'Donnell
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Christensen
authors.forename: Charles
authors.initials: C
authors.lastname: Nicholson
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Iliff
authors.forename: Takahiro
authors.initials: T
authors.lastname: Takano
authors.forename: Rashid
authors.initials: R
authors.lastname: Deane
authors.forename: Maiken
authors.initials: M
authors.lastname: Nedergaard
mesh_terms: D018674:Adrenergic Antagonists / Q000008:administration & dosage; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000502:physiology; D002540:Cerebral Cortex / Q000378:metabolism / Q000502:physiology; D002555:Cerebrospinal Fluid / Q000378:metabolism; D004058:Diffusion; D004569:Electroencephalography; D005110:Extracellular Space; D042541:Intracellular Space; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D011941:Receptors, Adrenergic / Q000378:metabolism; D012890:Sleep / Q000502:physiology*; D014851:Wakefulness / Q000502:physiology
chemical_list: D018674:Adrenergic Antagonists; D016229:Amyloid beta-Peptides; D000644:Quaternary Ammonium Compounds; D011941:Receptors, Adrenergic; C027917:tetramethylammonium