Title

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

Source Publication (e.g., journal title)

Scientific Reports

Authors

Allen K. Bourdon, University of Tennessee, KnoxvilleFollow
Giovanna Maria Spano, University of Wisconsin, Madison
William Marshall, University of Wisconsin, Madison
Michele Bellesi, University of Wisconsin, Madison
Giulio Tononi, University of Wisconsin, Madison
Pier Andrea Serra, University of Sassari, Italy
Helen A. Baghdoyan, University of Tennessee, Knoxville
Ralph Lydic, University of Tennessee, Knoxville
Shawn R. Campagna, University of Tennessee, KnoxvilleFollow
Chiara Cirelli, University of Wisconsin, Madison

Document Type

Article

Publication Date

7-25-2018

DOI

10.1038/s41598-018-29511-6

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.

Comments

This article was published openly thanks to the University of Tennessee Open Publishing Support Fund.

Licensed under a Creative Commons Attribution 4.0 International license.

Recommended Citation

Bourdon, Allen K.; Spano, Giovanna Maria; Marshall, William; Bellesi, Michele; Tononi, Giulio; Serra, Pier Andrea; Baghdoyan, Helen A.; Lydic, Ralph; Campagna, Shawn R.; and Cirelli, Chiara, "Metabolomic analysis of mouse prefrontal cortex reveals upregulated analytes during wakefulness compared to sleep" (2018) Scientific Reports volume 8, Article number: 11225. Doi: 10.1038/s41598-018-29511-6

Submission Type

Publisher's Version