Sleep drives metabolite clearance from the adult brain

Lulu Xie, Hongyi Kang, Qiwu Xu, Michael J. Chen, Yonghong Liao, Meenakshisundaram Thiyagarajan, John O'Donnell, Daniel J. Christensen, Charles Nicholson, Jeffrey J. Iliff, Takahiro Takano, Rashid Deane, Maiken Nedergaard

Research output: Contribution to journalArticle

1455 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)373-377
Number of pages5
JournalScience
Volume342
Issue number6156
DOIs
StatePublished - Jan 1 2013

ASJC Scopus subject areas

  • General

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    Xie, L., Kang, H., Xu, Q., Chen, M. J., Liao, Y., Thiyagarajan, M., O'Donnell, J., Christensen, D. J., Nicholson, C., Iliff, J. J., Takano, T., Deane, R., & Nedergaard, M. (2013). Sleep drives metabolite clearance from the adult brain. Science, 342(6156), 373-377. https://doi.org/10.1126/science.1241224