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Cited by 123Sleep and Wakefulness ResearchCircadian rhythm and melatoninSleep and Work-Related Fatigue

Lactate as a biomarker for sleep

Open access
Naylor, Erik, Aillon, Daniel V., Barrett, Brian S., Wilson, George S., Johnson, David A., Johnson, Donna A., Harmon, Hans P., Gabbert, Seth +1 more·2012·SLEEP
DOI 10.5665/sleep.2072PMC PMC3413798
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Abstract

STUDY OBJECTIVES: An ideal biomarker for sleep should change rapidly with sleep onset, remain at a detectably differential level throughout the sleep period, and exhibit a rapid change with waking. Currently, no molecular marker has been identified that exhibits all three properties. This study examined three substances (lactate, glucose, and glutamate) for suitability as a sleep biomarker. DESIGN: Using amperometric biosensor technology in conjunction with electroencephalograph (EEG) and electromyograph (EMG) monitoring, extracellular concentrations of lactate and glucose (Cohort 1) as well as lactate and glutamate (Cohort 2) were recorded over multiple sleep/wake cycles. PATIENTS OR PARTICIPANTS: There were 12 C57Bl/6J male mice (3-5 mo old). INTERVENTIONS: Sleep and waking transitions were identified using EEG recordings. Extracellular concentrations of lactate, glucose, and glutamate were evaluated before and during transition events as well as during extended sleep and during a 6-h sleep deprivation period. MEASUREMENTS AND RESULTS: Rapid and sustained increases in cortical lactate concentration (approximately 15 μM/min) were immediately observed upon waking and during rapid eye movement sleep. Elevated lactate concentration was also maintained throughout a 6-h period of continuous waking. A persistent and sustained decline in lactate concentration was measured during nonrapid eye movement sleep. Glutamate exhibited similar patterns, but with a much slower rise and decline (approximately 0.03 μM/min). Glucose concentration changes did not demonstrate a clear correlation with either sleep or wake. CONCLUSIONS: These findings indicate that extracellular lactate concentration is a reliable sleep/wake biomarker and can be used independently of the EEG signal.

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  • Elevated brain lactate and glutamate levels are associated with wakefulness and memory formation, which naturally require the processing of incoming sensory stimuli.

    “Elevated brain lactate and glutamate levels are associated with wakefulness and memory formation, which naturally require the processing of incoming sensory stimuli”

    From Perception is associated with the brain’s metabolic response to sensory stimulation (2022) · cites this paper as Naylor et al., 2012

    The Discussion reports that cortical lactate and glutamate rise upon waking and remain elevated during wakefulness. It also discusses evidence linking lactate transport to memory consolidation, but does not establish that elevated levels of both substances are associated with memory formation or with processing incoming sensory stimuli. (LLM, conf=0.86)

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Research works printed but not linked: 3

  1. [18]18. Shimizu H, Tabushi K, Hishikawa Y, Kakimoto Y, Kaneko Z. Concentra -tion of lactic acid in rat brain during natural sleep. Nature 1966;212:936-7.
  2. [26]26. Magistretti PJ, Pellerin L, Rothman DL, Shulman RG. Energy on de -mand. Science 1999;283:496-7.
  3. [53]53. Naylor E, Aillon D, Petillo PA. Simultaneous measurement of EEG/EMG and glutamate during normal sleep and sleep deprivation in a mouse model. Paper presented at: Monitoring Molecules in Neuroscience. Proceed -ings of the 13th International Conference on In Vivo Methods; 2010 Sept 12-16; Brussels, Belgium.

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Authors
Naylor, E., Aillon, D. V., Barrett, B. S., Wilson, G. S., Johnson, D. A., Johnson, D. A., Harmon, H. P., Gabbert, S., & Petillo, P. A.
Affiliations
  • Pinnacle Technology (US)
  • University of Kansas (US)
Corresponding author
  • Naylor, Erik
  • Petillo, Peter A.
ORCID
Venue
SLEEP
Publisher
Oxford University Press (OUP)
Published
2012-09-01
Volume
35
Issue
9
Pages
1209-22
ISSN
  • 0161-8105 (ISSN-L)
  • 1550-9109
DOI
10.5665/sleep.2072
PMC
PMC3413798
OpenAlex
W2083777706
Cited by
112
References
52
Citations by year
2026: 6 · 2025: 12 · 2024: 11 · 2023: 10 · 2022: 7 · 2021: 11 · 2020: 7 · 2019: 5 · 2018: 9 · 2017: 9 · 2016: 5 · 2015: 7 · 2014: 4 · 2013: 6 · 2012: 3
FWCI
3.27
Type
journal article
Language
en
Open access
Locations
  • SLEEP (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r44mh076318-03)
  • Defense Advanced Research Projects Agency
  • National Institute of Mental Health (5R44MH076318-03, R43MH076318)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
Keywords
lactate, sleep biomarkers, sleep-wake transition, extracellular lactate, glutamate, glucose, sleep deprivation, REM sleep, NREM sleep, amperometric biosensor, mice
MeSH terms
Animals, Cerebral Cortex, Electroencephalography, Electromyography, Glucose, Male, Mice, Inbred C57BL, Sleep, Sleep Deprivation, Sleep Stages, Wakefulness, Biomarkers, Glutamic Acid, Lactic Acid, Mice

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