Glutamatergic and GABAergic energy metabolism measured in the rat brain by 13C NMR spectroscopy at 14.1 T
Article first published online: 27 JUN 2013
© 2013 International Society for Neurochemistry
Journal of Neurochemistry
Volume 126, Issue 5, pages 579–590, September 2013
How to Cite
J. Neurochem. (2013) 126, 579–590.
- Issue published online: 23 AUG 2013
- Article first published online: 27 JUN 2013
- Accepted manuscript online: 8 JUN 2013 06:42AM EST
- Manuscript Accepted: 6 JUN 2013
- Manuscript Revised: 5 JUN 2013
- Manuscript Received: 24 JAN 2013
- Swiss National Science Foundation. Grant Number: 131087
- Centre d'Imagerie BioMédicale (CIBM) of the UNIL, UNIGE, HUG, CHUV, EPFL the Leenaards and Jeantet Foundations
- 13C NMR;
- GABA ;
Energy metabolism supports both inhibitory and excitatory neurotransmission processes. This study investigated the specific contribution of astrocytic metabolism to γ-aminobutyric acid (GABA) synthesis and inhibitory GABAergic neurotransmission that remained to be ilucidated in vivo. Therefore, we measured 13C incorporation into brain metabolites by dynamic 13C nuclear magnetic resonance spectroscopy at 14.1 T in rats under α-chloralose anaesthesia during infusion of [1,6-13C]glucose. The enhanced sensitivity at 14.1 T allowed to quantify incorporation of 13C into the three aliphatic carbons of GABA non-invasively. Metabolic fluxes were determined with a mathematical model of brain metabolism comprising glial, glutamatergic and GABAergic compartments. GABA synthesis rate was 0.11 ± 0.01 μmol/g/min. GABA-glutamine cycle was 0.053 ± 0.003 μmol/g/min and accounted for 22 ± 1% of total neurotransmitter cycling between neurons and glia. Cerebral glucose oxidation was 0.47 ± 0.02 μmol/g/min, of which 35 ± 1% and 7 ± 1% was diverted to the glutamatergic and GABAergic tricarboxylic acid cycles, respectively. The remaining fraction of glucose oxidation was in glia, where 12 ± 1% of the TCA cycle flux was dedicated to oxidation of GABA. 16 ± 2% of glutamine synthesis was provided to GABAergic neurons. We conclude that substantial metabolic activity occurs in GABAergic neurons and that glial metabolism supports both glutamatergic and GABAergic neurons in the living rat brain.
We performed 13C NMR spectroscopy in vivo at high magnetic field (14.1 T) upon administration of [1,6-13C]glucose. This allowed to measure 13C incorporation into the three aliphatic carbons of GABA in the rat brain, in addition to those of glutamate, glutamine and aspartate. These data were then modelled to determine fluxes of energy metabolism in GABAergic and glutamatergic neurons and glial cells.