Journal
JOURNAL OF NEUROSCIENCE
Volume 24, Issue 50, Pages 11273-11279Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.3564-04.2004
Keywords
NMR; brain; C-13; C-14; awake; rat; metabolic modeling
Categories
Funding
- NIDDK NIH HHS [R01 DK034738, DK34738, R56 DK034738] Funding Source: Medline
- NINDS NIH HHS [NS38672, R01 NS038672] Funding Source: Medline
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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.
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