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.

睡眠已经发展成为一种普遍的核心功能，可以实现恢复性的生物过程。目前尚不清楚大脑睡眠状态所需的代谢变化的详细知识。在这里，我们对四个小鼠大脑区域进行了深入的代谢分析，并发现了区域特异性的昼夜节律变化。与氧化应激相关的代谢物在睡眠期间发生改变，包括酰基肉碱、羟基化脂肪酸、酚类化合物和含硫醇的代谢物。这些发现提供了大脑能量代谢发生显着代谢转变的分子证据。观察到先前与昼夜节律功能无关的脑代谢物的特定改变，包括微生物组衍生的代谢物麦角硫因，表明其具有调节功能。伪肽β-柠檬酰谷氨酸与大脑发育有关，我们现在发现了一种以前未知的区域异构体。这些受昼夜节律改变的代谢物代表了对潜在代谢过程及其功能的假设驱动研究的基础。