Differential regulation of oxidative stress, microbiota-derived, and energy metabolites in the mouse brain during sleep

Author:

Vallianatou Theodosia1,Lin Weifeng1ORCID,Bèchet Nicholas B23,Correia Mario SP1ORCID,Shanbhag Nagesh C23,Lundgaard Iben23ORCID,Globisch Daniel1ORCID

Affiliation:

1. Department of Chemistry-BMC, Science for Life Laboratory, Uppsala University, Uppsala, Sweden

2. Department of Experimental Medical Science, Lund University, Lund University, Lund, Sweden

3. Wallenberg Centre for Molecular Medicine, Lund University, Lund University, Lund, Sweden

Abstract

Sleep has evolved as a universal core function to allow for restorative biological processes. Detailed knowledge of metabolic changes necessary for the sleep state in the brain is missing. Herein, we have performed an in-depth metabolic analysis of four mouse brain regions and uncovered region-specific circadian variations. Metabolites linked to oxidative stress were altered during sleep including acylcarnitines, hydroxylated fatty acids, phenolic compounds, and thiol-containing metabolites. These findings provide molecular evidence of a significant metabolic shift of the brain energy metabolism. Specific alterations were observed for brain metabolites that have previously not been associated with a circadian function including the microbiome-derived metabolite ergothioneine that suggests a regulatory function. The pseudopeptide β-citryl-glutamate has been linked to brain development and we have now discovered a previously unknown regioisomer. These metabolites altered by the circadian rhythm represent the foundation for hypothesis-driven studies of the underlying metabolic processes and their function.

Publisher

SAGE Publications

Subject

Cardiology and Cardiovascular Medicine,Neurology (clinical),Neurology

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