Glutamatergic Neurotransmission and Neuronal Glucose Oxidation Are Coupled During Intense Neuronal Activation.

Summary¹³C nuclear magnetic resonance (NMR) experiments have previously shown that glutamatergic neurotransmitter flux (V_{cycle(Glu/Gln)}) changes proportionately with neuronal glucose oxidation (CMR_glc(ox)N) in the nonactivated cortex of anesthetized rats. Positron Emission Tomography measurements of glucose and oxygen uptake during sensory stimulation had shown that the incremental glucose utilization is greater than oxygen leading to the suggestion that the energy required for stimulated neuronal activity arises from nonoxidative glucose metabolism. In this study, the authors used spatially localized ¹H-observed, ¹³C-edited NMR spectroscopy during an infusion of [1,6-¹³C₂]glucose to assess the relationship between changes in V_{cycle(Glu/Gln)} and glucose utilization (CMR_glc(ox)N and CMR_glc(nonox)) during the intense cortical activity associated with bicuculline-induced seizures. Metabolic fluxes were determined by model-based analysis of the ¹³C-enrichment time courses of glutamate-C4 and glutamine-C4 (CMR_glc(ox)N, V_{cycle(Glu/Gln)}) and lactate-C3 (CMR_glc(nonox)). The exchange rate between α-ketoglutarate and glutamate was found to be significantly faster than TCA cycle flux both for control (41 μmol·g⁻¹·min⁻¹; 95% CI, 5 to 109 μmol·g⁻¹·min⁻¹) and during seizures (21 μmol·g⁻¹·min⁻¹; 95% CI, 4.4 to 51.8 μmol·g⁻¹·min⁻¹). During seizures, total glucose utilization (CMR_{glc(ox+nonox)}) increased substantially (466% between 0 and 6 minutes; 277% between 6 and 55 minutes). Glucose oxidation (CMR_glc(ox)N) also increased (214%; from 0.26 ± 0.02 to 0.57 ± 0.07 μmol·g⁻¹·min⁻¹) but to a lesser degree, resulting in a large increase in cortical lactate concentration. V_{cycle(Glu/Gln)} increased 233% (from 0.22 ± 0.04 to 0.52 ± 0.07 μmol·g⁻¹·min⁻¹), which was similar to the increase in glucose oxidation. The value of V_{cycle(Glu/Gln)} and CMR_glc(ox)N obtained here lie on the line predicted in a previous study. These results indicate that neuronal glucose oxidation and not total glucose utilization is coupled to the glutamate/glutamine cycle during intense cortical activation.Journal of Cerebral Blood Flow & Metabolism (2004) 24, 972–985; doi:10.1097/01.WCB.0000126234.16188.71 [ABSTRACT FROM AUTHOR]