Metabolomic analysis of mouse prefrontal cortex reveals upregulated analytes during wakefulness compared to sleep

Allen K. Bourdon, Giovanna Maria Spano, William Marshall, Michele Bellesi, Giulio Tononi, Pier Andrea Serra, Helen Baghdoyan, Ralph Lydic, Shawn R. Campagna, Chiara Cirelli

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

By identifying endogenous molecules in brain extracellular fluid metabolomics can provide insight into the regulatory mechanisms and functions of sleep. Here we studied how the cortical metabolome changes during sleep, sleep deprivation and spontaneous wakefulness. Mice were implanted with electrodes for chronic sleep/wake recording and with microdialysis probes targeting prefrontal and primary motor cortex. Metabolites were measured using ultra performance liquid chromatography-high resolution mass spectrometry. Sleep/wake changes in metabolites were evaluated using partial least squares discriminant analysis, linear mixed effects model analysis of variance, and machine-learning algorithms. More than 30 known metabolites were reliably detected in most samples. When used by a logistic regression classifier, the profile of these metabolites across sleep, spontaneous wake, and enforced wake was sufficient to assign mice to their correct experimental group (pair-wise) in 80–100% of cases. Eleven of these metabolites showed significantly higher levels in awake than in sleeping mice. Some changes extend previous findings (glutamate, homovanillic acid, lactate, pyruvate, tryptophan, uridine), while others are novel (D-gluconate, N-acetyl-beta-alanine, N-acetylglutamine, orotate, succinate/methylmalonate). The upregulation of the de novo pyrimidine pathway, gluconate shunt and aerobic glycolysis may reflect a wake-dependent need to promote the synthesis of many essential components, from nucleic acids to synaptic membranes.

Original languageEnglish (US)
Article number11225
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

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Metabolomics
Wakefulness
Prefrontal Cortex
Sleep
beta-Alanine
Synaptic Membranes
Homovanillic Acid
Implanted Electrodes
Sleep Deprivation
Metabolome
Uridine
Extracellular Fluid
Microdialysis
Motor Cortex
Succinic Acid
Discriminant Analysis
Glycolysis
Least-Squares Analysis
Pyruvic Acid
Tryptophan

All Science Journal Classification (ASJC) codes

  • General

Cite this

Bourdon, A. K., Spano, G. M., Marshall, W., Bellesi, M., Tononi, G., Serra, P. A., ... Cirelli, C. (2018). Metabolomic analysis of mouse prefrontal cortex reveals upregulated analytes during wakefulness compared to sleep. Scientific Reports, 8(1), [11225]. https://doi.org/10.1038/s41598-018-29511-6

Metabolomic analysis of mouse prefrontal cortex reveals upregulated analytes during wakefulness compared to sleep. / Bourdon, Allen K.; Spano, Giovanna Maria; Marshall, William; Bellesi, Michele; Tononi, Giulio; Serra, Pier Andrea; Baghdoyan, Helen; Lydic, Ralph; Campagna, Shawn R.; Cirelli, Chiara.

In: Scientific Reports, Vol. 8, No. 1, 11225, 01.12.2018.

Research output: Contribution to journalArticle

Bourdon, Allen K. ; Spano, Giovanna Maria ; Marshall, William ; Bellesi, Michele ; Tononi, Giulio ; Serra, Pier Andrea ; Baghdoyan, Helen ; Lydic, Ralph ; Campagna, Shawn R. ; Cirelli, Chiara. / Metabolomic analysis of mouse prefrontal cortex reveals upregulated analytes during wakefulness compared to sleep. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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