The DOI matches its Crossref record; 77 of the 77 references it cites were found in a registry or an index.
Glymphatic clearance controls state-dependent changes in brain lactate concentration
Open accessAbstract
Brain lactate concentration is higher during wakefulness than in sleep. However, it is unknown why arousal is linked to an increase in brain lactate and why lactate declines within minutes of sleep. Here, we show that the glymphatic system is responsible for state-dependent changes in brain lactate concentration. Suppression of glymphatic function via acetazolamide treatment, cisterna magna puncture, aquaporin 4 deletion, or changes in body position reduced the decline in brain lactate normally observed when awake mice transition into sleep or anesthesia. Concurrently, the same manipulations diminished accumulation of lactate in cervical, but not in inguinal lymph nodes when mice were anesthetized. Thus, our study suggests that brain lactate is an excellent biomarker of the sleep–wake cycle and increases further during sleep deprivation, because brain lactate is inversely correlated with glymphatic-lymphatic clearance. This analysis provides fundamental new insight into brain energy metabolism by demonstrating that glucose that is not fully oxidized can be exported as lactate via glymphatic-lymphatic fluid transport.
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Cites
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Self-citationSleep Drives Metabolite Clearance from the Adult Brain
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Self-citationStructural and functional features of central nervous system lymphatic vessels
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Brain energy metabolism: focus on Astrocyte-neuron metabolic cooperation
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A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules
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Amyloid-β Dynamics Are Regulated by Orexin and the Sleep-Wake Cycle
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Cited by
Verkhratsky, A., & Nedergaard, M. (2018) · Physiological Reviews · doi:10.1152/physrev.00042.2016 · Cited by 1,678
Self-citationThe glymphatic pathway in neurological disorders.
Rasmussen, M. K., Mestre, H., & Nedergaard, M. (2018) · The Lancet Neurology · doi:10.1016/s1474-4422(18)30318-1 · Cited by 1,560
Self-citationAquaporin-4-dependent glymphatic solute transport in the rodent brain
Mestre, H., Hablitz, L. M., Xavier, A. L., Feng, W., Zou, W., Pu, T., Monai, H., Murlidharan, G., Castellanos Rivera, R. M., Simon, M. J., et al. (2018) · eLife · doi:10.7554/elife.40070 · Cited by 738
Self-citationImpaired glymphatic function and clearance of tau in an Alzheimer’s disease model
Harrison, I. F., Ismail, O., Machhada, A., Colgan, N., Ohene, Y., Nahavandi, P., Ahmed, Z., Fisher, A., Meftah, S., Murray, T. K., et al. (2020) · Brain · doi:10.1093/brain/awaa179 · Cited by 672
Understanding the functions and relationships of the glymphatic system and meningeal lymphatics
Louveau, A., Plog, B. A., Antila, S., Alitalo, K., Nedergaard, M., & Kipnis, J. (2017) · Journal of Clinical Investigation · doi:10.1172/jci90603 · Cited by 640
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Metadata
- Authors
- Lundgaard, I., Lu, M. L., Yang, E., Peng, W., Mestre, H., Hitomi, E., Deane, R., & Nedergaard, M.
- Venue
- Journal of Cerebral Blood Flow & Metabolism
- Publisher
- SAGE Publications
- Published
- 2016-08-08
- Volume
- 37
- Issue
- 6
- Pages
- 2112-2124
- ISSN
- 0271-678X (ISSN-L)
- 1559-7016
- OpenAlex
- W2480915756
- Cited by
- 299
- References
- 77
- FWCI
- 12.54
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Lundgaard, I., Lu, M. L., Yang, E., Peng, W., Mestre, H., Hitomi, E., Deane, R., & Nedergaard, M. (2017). Glymphatic clearance controls state-dependent changes in brain lactate concentration. Journal of Cerebral Blood Flow & Metabolism. https://doi.org/10.1177/0271678x16661202
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