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Mechanisms underlying neonate-specific metabolic effects of volatile anesthetics.

ABSTRACT: Volatile anesthetics (VAs) are widely used in medicine, but the mechanisms underlying their effects remain ill-defined. Though routine anesthesia is safe in healthy individuals, instances of sensitivity are well documented, and there has been significant concern regarding the impact of VAs on neonatal brain development. Evidence indicates that VAs have multiple targets, with anesthetic and non-anesthetic effects mediated by neuroreceptors, ion channels, and the mitochondrial electron transport chain. Here, we characterize an unexpected metabolic effect of VAs in neonatal mice. Neonatal blood β-hydroxybutarate (β-HB) is rapidly depleted by VAs at concentrations well below those necessary for anesthesia. β-HB in adults, including animals in dietary ketosis, is unaffected. Depletion of β-HB is mediated by citrate accumulation, malonyl-CoA production by acetyl-CoA carboxylase, and inhibition of fatty acid oxidation. Adults show similar significant changes to citrate and malonyl-CoA, but are insensitive to malonyl-CoA, displaying reduced metabolic flexibility compared to younger animals.

SUBMITTER: Stokes J

PROVIDER: S-EPMC8291971 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Mechanisms underlying neonate-specific metabolic effects of volatile anesthetics.

Stokes Julia J Freed Arielle A Bornstein Rebecca R Su Kevin N KN Snell John J Pan Amanda A Sun Grace X GX Park Kyung Yeon KY Jung Sangwook S Worstman Hailey H Johnson Brittany M BM Morgan Philip G PG Sedensky Margaret M MM Johnson Simon C SC

eLife 20210713

Volatile anesthetics (VAs) are widely used in medicine, but the mechanisms underlying their effects remain ill-defined. Though routine anesthesia is safe in healthy individuals, instances of sensitivity are well documented, and there has been significant concern regarding the impact of VAs on neonatal brain development. Evidence indicates that VAs have multiple targets, with anesthetic and non-anesthetic effects mediated by neuroreceptors, ion channels, and the mitochondrial electron transport c ...[more]

PMID: 34254587

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Dataset Information

Mechanisms underlying neonate-specific metabolic effects of volatile anesthetics.

Publications

Mechanisms underlying neonate-specific metabolic effects of volatile anesthetics.

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