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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2018-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-018-29511-6 |
| _version_ | 1830286926293237760 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T04:07:16Z |
| format | Article |
| id | doaj.art-a457f0f7191f427aa96a87048d92199f |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-19T04:07:16Z |
| publishDate | 2018-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-a457f0f7191f427aa96a87048d92199f2022-12-21T20:36:29ZengNature PortfolioScientific Reports2045-23222018-07-018111710.1038/s41598-018-29511-6Metabolomic analysis of mouse prefrontal cortex reveals upregulated analytes during wakefulness compared to sleepAllen K. Bourdon0Giovanna Maria Spano1William Marshall2Michele Bellesi3Giulio Tononi4Pier Andrea Serra5Helen A. Baghdoyan6Ralph Lydic7Shawn R. Campagna8Chiara Cirelli9Department of Chemistry, University of TennesseeDepartment of Psychiatry, University of Wisconsin, MadisonDepartment of Psychiatry, University of Wisconsin, MadisonDepartment of Psychiatry, University of Wisconsin, MadisonDepartment of Psychiatry, University of Wisconsin, MadisonDepartment of Clinical and Experimental Medicine, University of SassariDepartment of Anesthesiology and Psychology, University of TennesseeDepartment of Anesthesiology and Psychology, University of TennesseeDepartment of Chemistry, University of TennesseeDepartment of Psychiatry, University of Wisconsin, MadisonAbstract 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.https://doi.org/10.1038/s41598-018-29511-6 |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-018-29511-6 |
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