The Campagna Lab published their work “Isoflurane anesthesia disrupts the cortical metabolome” in a collaborative piece in the Journal of Neurophysiology (JNP).
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.