Sleep drives metabolite clearance from the adult brain

Science. 2013 Oct 18;342(6156):373-7. doi: 10.1126/science.1241224.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adrenergic Antagonists / administration & dosage
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Brain / metabolism*
  • Brain / physiology
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / physiology
  • Cerebrospinal Fluid / metabolism
  • Diffusion
  • Electroencephalography
  • Extracellular Space
  • Intracellular Space
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neurodegenerative Diseases / metabolism*
  • Quaternary Ammonium Compounds / chemistry
  • Receptors, Adrenergic / metabolism
  • Sleep / physiology*
  • Wakefulness / physiology


  • Adrenergic Antagonists
  • Amyloid beta-Peptides
  • Quaternary Ammonium Compounds
  • Receptors, Adrenergic
  • tetramethylammonium