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

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...

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Autores principales:	Allen K. Bourdon, Giovanna Maria Spano, William Marshall, Michele Bellesi, Giulio Tononi, Pier Andrea Serra, Helen A. Baghdoyan, Ralph Lydic, Shawn R. Campagna, Chiara Cirelli
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a457f0f7191f427aa96a87048d92199f
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spelling	oai:doaj.org-article:a457f0f7191f427aa96a87048d92199f2021-12-02T15:09:04ZMetabolomic analysis of mouse prefrontal cortex reveals upregulated analytes during wakefulness compared to sleep10.1038/s41598-018-29511-62045-2322https://doaj.org/article/a457f0f7191f427aa96a87048d92199f2018-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-29511-6https://doaj.org/toc/2045-2322Abstract 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.Allen K. BourdonGiovanna Maria SpanoWilliam MarshallMichele BellesiGiulio TononiPier Andrea SerraHelen A. BaghdoyanRalph LydicShawn R. CampagnaChiara CirelliNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-17 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Allen K. Bourdon Giovanna Maria Spano William Marshall Michele Bellesi Giulio Tononi Pier Andrea Serra Helen A. Baghdoyan Ralph Lydic Shawn R. Campagna Chiara Cirelli Metabolomic analysis of mouse prefrontal cortex reveals upregulated analytes during wakefulness compared to sleep
description	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.
format	article
author	Allen K. Bourdon Giovanna Maria Spano William Marshall Michele Bellesi Giulio Tononi Pier Andrea Serra Helen A. Baghdoyan Ralph Lydic Shawn R. Campagna Chiara Cirelli
author_facet	Allen K. Bourdon Giovanna Maria Spano William Marshall Michele Bellesi Giulio Tononi Pier Andrea Serra Helen A. Baghdoyan Ralph Lydic Shawn R. Campagna Chiara Cirelli
author_sort	Allen K. Bourdon
title	Metabolomic analysis of mouse prefrontal cortex reveals upregulated analytes during wakefulness compared to sleep
title_short	Metabolomic analysis of mouse prefrontal cortex reveals upregulated analytes during wakefulness compared to sleep
title_full	Metabolomic analysis of mouse prefrontal cortex reveals upregulated analytes during wakefulness compared to sleep
title_fullStr	Metabolomic analysis of mouse prefrontal cortex reveals upregulated analytes during wakefulness compared to sleep
title_full_unstemmed	Metabolomic analysis of mouse prefrontal cortex reveals upregulated analytes during wakefulness compared to sleep
title_sort	metabolomic analysis of mouse prefrontal cortex reveals upregulated analytes during wakefulness compared to sleep
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/a457f0f7191f427aa96a87048d92199f
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Metabolomic analysis of mouse prefrontal cortex reveals upregulated analytes during wakefulness compared to sleep

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