Isoflurane anesthesia disrupts the cortical metabolome

Aaron G. Baer, Allen K. Bourdon, Joshua M. Price, Shawn R. Campagna, Daniel A. Jacobson, Helen A. Baghdoyan, Ralph Lydic

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Baer AG, Bourdon AK, Price JM, Campagna SR, Jacobson DA, Baghdoyan HA, Lydic R. Isoflurane anesthesia disrupts the cortical metabolome. J Neurophysiol 124: 2012-2021, 2020. First published October 28, 2020; doi:10.1152/jn.00375.2020.-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 (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) 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. NEW & NOTEWORTHY 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.

Original languageEnglish
Pages (from-to)2012-2021
Number of pages10
JournalJournal of Neurophysiology
Volume124
Issue number6
DOIs
StatePublished - Dec 2020

Funding

This paper has been coauthored by UT-Battelle, LLC, under Contract No. DE-AC05-00OR22725 with the U.S. Department of Energy. The United States Government retains and the publisher, by accepting the article for publication, acknowledges that the United States Government retains a nonexclusive, paid-up, irrevocable, worldwide license to publish or reproduce the published form of this paper, or allow others to do so, for United States Government purposes. The Department of Energy will provide public access to these results of federally sponsored research in accordance with the DOE Public Access Plan (https:// energy.gov/downloads/doe-public-access-plan). This work was supported by Departments of Anesthesiology and Psychology, University of Tennessee, Knoxville, TN, and National Heart, Lung, and Blood Institute Grant HL-65272 (R.L.).

Keywords

  • In vivo microdialysis
  • Liquid chromatography-dual mass spectrometry
  • Prefrontal cortex
  • States of consciousness
  • Untargeted metabolomics

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