Neuroglial Metabolism in the Awake Rat Brain: CO2Fixation Increases with Brain Activity

Abstract

Glial cells are thought to supply energy for neurotransmission by increasing nonoxidative glycolysis; however, oxidative metabolism in glia may also 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 with¹⁴C-bicarbonate and [1-¹³C]glucose for up to 1 hr. The¹⁴C and¹³C labeling of glutamate, glutamine, and aspartate was measured at five time points in tissue extracts using scintillation counting and¹³C nuclear magnetic resonance of the chromatographically separated amino acids. The isotopic¹³C enrichment of glutamate and glutamine was different, suggesting significant rates of glial metabolism compared with the glutamate-glutamine cycle. Modeling the¹³C-labeling time courses alone and with¹⁴C confirmed significant glial TCA cycle activity ( \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \(V_{\mathrm{PDH}}^{(\mathrm{g})},{\sim}0.5\) μmol · gm^-1· min^-1) relative to the glutamate-glutamine cycle (V_NT) (∼0.5-0.6 μmol · gm^-1· min^-1). The glial TCA cycle rate was ∼30% of total TCA cycle activity. A high pyruvate carboxylase rate (V_PC, ∼0.14-0.18 μmol · 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 same¹³C-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.