title: Lactate as a biomarker for sleep.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  There were 12 C57Bl/6J male mice (3-5 mo old).
  
  
  METHODS
  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.
  
  
  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.
authors.affiliation: Pinnacle Technology, Inc., Lawrence, KS 66046, USA. e-naylor@pinnaclet.com
authors.forename: Erik
authors.initials: E
authors.lastname: Naylor
authors.forename: Daniel V
authors.initials: DV
authors.lastname: Aillon
authors.forename: Brian S
authors.initials: BS
authors.lastname: Barrett
authors.forename: George S
authors.initials: GS
authors.lastname: Wilson
authors.forename: David A
authors.initials: DA
authors.lastname: Johnson
authors.forename: Donna A
authors.initials: DA
authors.lastname: Johnson
authors.forename: Hans P
authors.initials: HP
authors.lastname: Harmon
authors.forename: Seth
authors.initials: S
authors.lastname: Gabbert
authors.forename: Peter A
authors.initials: PA
authors.lastname: Petillo
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D004569:Electroencephalography / Q000379:methods; D004576:Electromyography / Q000379:methods; D005947:Glucose / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012890:Sleep / Q000502:physiology*; D012892:Sleep Deprivation / Q000378:metabolism; D012894:Sleep Stages; D014851:Wakefulness
chemical_list: D015415:Biomarkers; D019344:Lactic Acid; D018698:Glutamic Acid; D005947:Glucose