Neuroglial metabolism in the awake rat brain:: CO2 fixation increases with brain activity

Glial cells are thought to supply energy for neurotransmission by increasing nonoxidative glycolysis; however, oxidative metabolism in gliamayalso contribute to increased brain activity. To study glial contribution to cerebral energy metabolism in the unanesthetized state, we measured neuronal and glial metabolic fluxes in the awake rat brain by using a double isotopic-labeling technique and a two-compartment mathematical model of neurotransmitter metabolism. Rats (n = 23) were infused simultaneously with C-14-bicarbonate and [1-C-13] glucose for up to 1 hr. The C-14 and C-13 labeling of glutamate, glutamine, and aspartate was measured at five time points in tissue extracts using scintillation counting and C-13 nuclear magnetic resonance of the chromatographically separated amino acids. The isotopic C-13 enrichment of glutamate and glutamine was different, suggesting significant rates of glial metabolism compared with the glutamate-glutamine cycle. Modeling the C-13- labeling time courses alone and with C-14 confirmed significant glial TCA cycle activity (V-PDH((g)), similar to0.5 mumol . gm(-1) . min(-1)) relative to the glutamate-glutamine cycle (V-NT) (similar to0.5-0.6 mumol . gm(-1) . min(-1)). The glial TCA cycle rate was similar to30% of total TCA cycle activity. A high pyruvate carboxylase rate (V-PC, similar to0.14-0.18 mumol . gm(-1) . min(-1)) contributed to the glial TCA cycle flux. This anaplerotic rate in the awake rat brain was severalfold higher than under deep pentobarbital anesthesia, measured previously in our laboratory using the same C-13-labeling technique. We postulate that the high rate of anaplerosis in awake brain is linked to brain activity by maintaining glial glutamine concentrations during increased neurotransmission.