Rates of pyruvate carboxylase, glutamate and GABA neurotransmitter cycling, and glucose oxidation in multiple brain regions of the awake rat using a combination of [2-13C]/[1-13C]glucose infusion and 1H-[13C]NMR ex vivo

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Anaplerosis occurs predominately in astroglia through the action of pyruvate carboxylase (PC). The rate of PC (Vpc) has been reported for cerebral cortex (or whole brain) of awake humans and anesthetized rodents, but regional brain rates remain largely unknown and, hence, were subjected to investigation in the current study. Awake male rats were infused with either [2-13C]glucose or [1-13C]glucose (n = 27/30) for 8, 15, 30, 60 or 120 min, followed by rapid euthanasia with focused-beam microwave irradiation to the brain. Blood plasma and extracts of cerebellum, hippocampus, striatum, and cerebral cortex were analyzed by 1H-[13C]-NMR to establish 13C-enrichment time courses for glutamate-C4,C3,C2, glutamine-C4,C3, GABA-C2,C3,C4 and aspartate-C2,C3. Metabolic rates were determined by fitting a three-compartment metabolic model (glutamatergic and GABAergic neurons and astroglia) to the eighteen time courses. Vpc varied by 44% across brain regions, being lowest in the cerebellum (0.087 ± 0.004 µmol/g/min) and highest in striatum (0.125 ± 0.009) with intermediate values in cerebral cortex (0.106 ± 0.005) and hippocampus (0.114 ± 0.005). Vpc constituted 13–19% of the oxidative glucose consumption rate. Combination of cerebral cortical data with literature values revealed a positive correlation between Vpc and the rates of glutamate/glutamine-cycling and oxidative glucose consumption, respectively, consistent with earlier observations.

Original languageEnglish
JournalJournal of Cerebral Blood Flow and Metabolism
Issue number8
Pages (from-to)1507–1523
Publication statusPublished - 2022

Bibliographical note

Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: LMM acknowledges the Department of Drug Design and Pharmacology (UCPH, Denmark) for granting of a PhD scholarship. This work was supported in part by NIH NIMH grants MH095104 and MH109159, NIH NIDDK grant R01 DK108283, NIH NIAAA grant R01 AA021984 and R21 AA028628, and a grant from Aase og Ejnar Danielsens Fond. Acknowledgements

Publisher Copyright:
© The Author(s) 2022.

    Research areas

  • Anaplerosis, cerebellum, cerebral cortex, hippocampus, striatum

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