Glutamatergic and GABAergic energy metabolism measured in the rat brain by ¹³C NMR spectroscopy at 14.1 T

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 GABA ergic neurotransmission that remained to be ilucidated in vivo . Therefore, we measured 13 C incorporation into brain metabolites by dynamic 13 C nuclear magnetic resonance spectroscopy at 14.1 T in rats under α‐chloralose anaesthesia during infusion of [1,6‐ 13 C]glucose. The enhanced sensitivity at 14.1 T allowed to quantify incorporation of 13 C into the three aliphatic carbons of GABA non‐invasively. Metabolic fluxes were determined with a mathematical model of brain metabolism comprising glial, glutamatergic and GABA ergic 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 GABA ergic 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 GABA ergic neurons. We conclude that substantial metabolic activity occurs in GABA ergic neurons and that glial metabolism supports both glutamatergic and GABA ergic neurons in the living rat brain. image We performed 13 C NMR spectroscopy in vivo at high magnetic field (14.1 T) upon administration of [1,6‐ 13 C]glucose. This allowed to measure 13 C 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.