Glymphatic clearance controls state-dependent changes in brain lactate concentration
(2017) In Journal of Cerebral Blood Flow and Metabolism 37(6). p.2112-2124- Abstract
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... (More)
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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- author
- Lundgaard, Iben LU ; Lu, Minh Lon ; Yang, Ezra ; Peng, Weiguo ; Mestre, Humberto ; Hitomi, Emi ; Deane, Rashid and Nedergaard, Maiken
- publishing date
- 2017-06-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Astrocytes, Cerebrospinal fluid, Glymphatic system, Lactate, Metabolism, Stroke
- in
- Journal of Cerebral Blood Flow and Metabolism
- volume
- 37
- issue
- 6
- pages
- 13 pages
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:27481936
- scopus:85019720596
- ISSN
- 0271-678X
- DOI
- 10.1177/0271678X16661202
- language
- English
- LU publication?
- no
- id
- b2af19d7-3edf-48c3-b8c4-cbc2aa24a990
- date added to LUP
- 2019-05-16 16:38:51
- date last changed
- 2024-05-01 07:16:10
@article{b2af19d7-3edf-48c3-b8c4-cbc2aa24a990,
abstract = {{<p>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.</p>}},
author = {{Lundgaard, Iben and Lu, Minh Lon and Yang, Ezra and Peng, Weiguo and Mestre, Humberto and Hitomi, Emi and Deane, Rashid and Nedergaard, Maiken}},
issn = {{0271-678X}},
keywords = {{Astrocytes; Cerebrospinal fluid; Glymphatic system; Lactate; Metabolism; Stroke}},
language = {{eng}},
month = {{06}},
number = {{6}},
pages = {{2112--2124}},
publisher = {{Nature Publishing Group}},
series = {{Journal of Cerebral Blood Flow and Metabolism}},
title = {{Glymphatic clearance controls state-dependent changes in brain lactate concentration}},
url = {{http://dx.doi.org/10.1177/0271678X16661202}},
doi = {{10.1177/0271678X16661202}},
volume = {{37}},
year = {{2017}},
}