Compartmentalized Cerebral Metabolism of [1,6-13C]Glucose Determined by in vivo13C NMR Spectroscopy at 14.1 T

Abstract

Cerebral metabolism is compartmentalized between neurons and glia. Although glial glycolysis is thought to largely sustain the energetic requirements of neurotransmission while oxidative metabolism takes place mainly in neurons, this hypothesis is matter of debate. The compartmentalization of cerebral metabolic fluxes can be determined by ¹³C nuclear magnetic resonance (NMR) spectroscopy upon infusion of ¹³C-enriched compounds, especially glucose. Rats under light α-chloralose anesthesia were infused with [1,6-¹³C]glucose and ¹³C enrichment in the brain metabolites was measured by ¹³C NMR spectroscopy with high sensitivity and spectral resolution at 14.1 T. This allowed determining ¹³C enrichment curves of amino acid carbons with high reproducibility and to reliably estimate cerebral metabolic fluxes (mean error of 8%). We further found that TCA cycle intermediates are not required for flux determination in mathematical models of brain metabolism. Neuronal tricarboxylic acid cycle rate (V_TCA) and neurotransmission rate (V_NT) were 0.45 ± 0.01 and 0.11 ± 0.01 μmol/g/min, respectively. Glial V_TCA was found to be 38 ± 3% of total cerebral oxidative metabolism, accounting for more than half of neuronal oxidative metabolism. Furthermore, glial anaplerotic pyruvate carboxylation rate (V_PC) was 0.069 ± 0.004 μmol/g/min, i.e., 25 ± 1% of the glial TCA cycle rate. These results support a role of glial cells as active partners of neurons during synaptic transmission beyond glycolytic metabolism.