Spatially resolved metabolomics and isotope tracing reveal dynamic metabolic responses of dentate granule neurons with acute stimulation.

Publisher: Springer Nature Country of Publication: Germany NLM ID: 101736592 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2522-5812 (Electronic) Linking ISSN: 25225812 NLM ISO Abbreviation: Nat Metab Subsets: MEDLINE

Original Publication: Berlin : Springer Nature, [2019]-

Dentate Gyrus*/physiology ; Neurons*; Mice ; Animals ; Cell Membrane ; Isotopes ; Metabolomics

Neuronal activity creates an intense energy demand that must be met by rapid metabolic responses. To investigate metabolic adaptations in the neuron-enriched dentate granule cell (DGC) layer within its native tissue environment, we employed murine acute hippocampal brain slices, coupled with fast metabolite preservation and followed by mass spectrometry (MS) imaging, to generate spatially resolved metabolomics and isotope-tracing data. Here we show that membrane depolarization induces broad metabolic changes, including increased glycolytic activity in DGCs. Increased glucose metabolism in response to stimulation is accompanied by mobilization of endogenous inosine into pentose phosphates via the action of purine nucleotide phosphorylase (PNP). The PNP reaction is an integral part of the neuronal response to stimulation, because inhibition of PNP leaves DGCs energetically impaired during recovery from strong activation. Performing MS imaging on brain slices bridges the gap between live-cell physiology and the deep chemical analysis enabled by MS.
(© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Update of: Res Sq. 2023 Jul 25;:. (PMID: 37546759)

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0 (Isotopes)

Date Created: 20231005 Date Completed: 20231031 Latest Revision: 20240406

20240406

PMC10626993

10.1038/s42255-023-00890-z

37798473