Glutamatergic Neurotransmission and Neuronal Glucose Oxidation are Coupled during Intense Neuronal Activation
Year: 2004
Type: article
Abstract: 13C nuclear magnetic resonance (NMR) experiments have previously shown that glutamatergic neurotransmitter flux (Vcycle(Glu/Gln)) changes proportionately with neuronal glucose oxidation (CMRglc(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 Vcycle(Glu/Gln) and glucose utilization (CMRglc(ox)N and CMRglc(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 (CMRglc(ox)N, Vcycle(Glu/Gln)) and lactate-C3 (CMRglc(nonox)). The exchange rate between alpha-ketoglutarate and glutamate was found to be significantly faster than TCA cycle flux both for control (41 micromol.g(-1).min(-1); 95% CI, 5 to 109 micromol.g(-1).min(-1)) and during seizures (21 micromol.g(-1).min(-1); 95% CI, 4.4 to 51.8 micromol.g(-1).min(-1)). During seizures, total glucose utilization (CMRglc(ox+nonox)) increased substantially (466% between 0 and 6 minutes; 277% between 6 and 55 minutes). Glucose oxidation (CMRglc(ox)N) also increased (214%; from 0.26 +/- 0.02 to 0.57 +/- 0.07 micromol.g(-1).min(-1)) but to a lesser degree, resulting in a large increase in cortical lactate concentration. Vcycle(Glu/Gln) increased 233% (from 0.22 +/- 0.04 to 0.52 +/- 0.07 micromol.g(-1).min(-1)), which was similar to the increase in glucose oxidation. The value of Vcycle(Glu/Gln) and CMRglc(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.
Institutions: Yale University, Soka University
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: bronze
Funders: National Alliance for Research on Schizophrenia and Depression, National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Institute of Biomedical Imaging and Bioengineering, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1304064820, G1663242702, G1735255276, G2033464147, G2418547450, G2815518252, G2848036350, G3062763842, G3742209472, Quantitative MR Imaging and Spectroscopy in Alcoholism, G73399757, NMR Studies of GABA Metabolism and Regulation in Vivo, G783836315, G894358835, Center for the Translational Neuroscience of Alcoholism
OpenAlex ID: W1965395380