Identifying similarities and differences in the brain metabolome during different states of consciousness has broad relevance for neuroscience and state-dependent autonomic function. This study focused on prefrontal cortex (PFC) as a brain region known to modulate states of consciousness. Anesthesia was used as a tool to eliminate wakefulness. Untargeted metabolomic analyses were performed on microdialysis samples obtained from mouse PFC during wakefulness and during isoflurane anesthesia. Analyses detected 2153 molecules, 91 of which could be identified. Analytes were grouped as detected during both wakefulness and anesthesia (n=61), and as unique to wakefulness (n=23) or anesthesia (n=7). Data were analyzed using univariate and multivariate approaches. Relative to wakefulness, during anesthesia there was a significant (q < 0.0001) four-fold change in 21 metabolites. During anesthesia 11 of these 21 molecules decreased and 10 increased. The Kyoto Encyclopedia of Genes and Genomes database was used to relate behavioral state specific changes in the metabolome to metabolic pathways. Relative to wakefulness, most of the amino acids and analogs measured were significantly decreased during isoflurane anesthesia. Nucleosides and analogs were significantly increased during anesthesia. Molecules associated with carbohydrate metabolism, maintenance of lipid membranes, and normal cell functions were significantly decreased during anesthesia. Significant state-specific changes also were discovered among molecules comprising lipids and fatty acids, monosaccharides, and organic acids. Considered together, these molecules regulate point to point transmission, volume conduction, and cellular metabolism. The results identify a novel ensemble of candidate molecules in PFC as putative modulators of wakefulness and the loss of wakefulness.

中文翻译：

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异氟醚麻醉破坏皮质代谢组

识别不同意识状态下大脑代谢组的异同与神经科学和状态依赖性自主神经功能具有广泛的相关性。这项研究的重点是前额叶皮层 (PFC) 作为已知调节意识状态的大脑区域。麻醉被用作消除觉醒的工具。在清醒和异氟醚麻醉期间对从小鼠 PFC 获得的微透析样品进行非靶向代谢组学分析。分析检测到 2153 个分子，其中 91 个可以被识别。分析物被分组为在清醒和麻醉期间检测到的 (n=61)，以及清醒 (n=23) 或麻醉 (n=7) 所特有的。使用单变量和多变量方法分析数据。相对于清醒，麻醉期间存在显着性（q < 0. 0001) 21 种代谢物的四倍变化。在麻醉期间，这 21 个分子中有 11 个减少，10 个增加。京都基因和基因组百科全书数据库用于将代谢组中的行为状态特定变化与代谢途径联系起来。相对于清醒，在异氟醚麻醉期间，测量的大多数氨基酸和类似物显着减少。核苷和类似物在麻醉期间显着增加。与碳水化合物代谢、脂质膜维持和正常细胞功能相关的分子在麻醉期间显着减少。在包含脂质和脂肪酸、单糖和有机酸的分子中也发现了显着的状态特异性变化。综合考虑，这些分子调节点对点传输、体积传导、和细胞代谢。结果确定了 PFC 中候选分子的新集合，作为推定的觉醒和觉醒丧失调节剂。