Department of Anesthesiology, University of Tennessee Medical Center, Knoxville, Tennessee.
Department of Chemistry, University of Tennessee, Knoxville, Tennessee.
J Neurophysiol. 2020 Dec 1;124(6):2012-2021. doi: 10.1152/jn.00375.2020. Epub 2020 Oct 28.
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 the 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 2,153 molecules, 91 of which could be identified. Analytes were grouped as detected during both wakefulness and anesthesia ( = 61) and as unique to wakefulness ( = 23) or anesthesia ( = 7). Data were analyzed using univariate and multivariate approaches. Relative to wakefulness, during anesthesia there was a significant ( < 0.0001) fourfold 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 were also 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. The loss of wakefulness caused by a single concentration of isoflurane significantly altered levels of interrelated metabolites in the prefrontal cortex. The results support the interpretation that states of consciousness reflect dynamic interactions among cortical neuronal networks involving a humbling number of molecules that comprise the brain metabolome.
鉴定不同意识状态下大脑代谢组的相似性和差异性，对神经科学和状态依赖的自主功能具有广泛的意义。本研究集中在大脑前额叶皮层（PFC），作为一个已知调节意识状态的大脑区域。使用麻醉作为消除觉醒的工具。在清醒状态和异氟烷麻醉期间，对从小鼠 PFC 获得的微透析样本进行非靶向代谢组分析。分析检测到 2153 种分子，其中 91 种可以鉴定。分析物被分为在清醒和麻醉期间都被检测到的（=61）和仅在清醒（=23）或麻醉（=7）时被检测到的。使用单变量和多变量方法分析数据。与清醒相比，在麻醉期间，有 21 种代谢物的相对变化有显著意义（<0.0001），有 4 倍。在麻醉期间，这 21 种分子中的 11 种减少，10 种增加。京都基因与基因组百科全书数据库用于将代谢组中与行为状态特异性变化相关的代谢途径与代谢途径相关联。与清醒相比，在异氟烷麻醉期间，测量的大多数氨基酸和类似物显著降低。核苷和类似物在麻醉期间显著增加。与脂质膜的维持、正常细胞功能相关的分子在麻醉期间显著减少。在脂质和脂肪酸、单糖和有机酸组成的分子中也发现了显著的状态特异性变化。综合考虑，这些分子调节点对点传递、容积传导和细胞代谢。这些结果确定了 PFC 中一组新的候选分子，作为觉醒和觉醒丧失的潜在调节剂。单一浓度异氟烷引起的觉醒丧失显著改变了前额叶皮层中相互关联的代谢物的水平。结果支持这样的解释，即意识状态反映了涉及组成大脑代谢组的分子数量相当少的皮质神经元网络之间的动态相互作用。
