Glutamatergic and GABAergic Neurotransmitter Cycling and Energy Metabolism in Rat Cerebral Cortex during Postnatal Development

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Abstract
The contribution of glutamatergic and -aminobutyric acid (GABA)ergic neurons to oxidative energy metabolism and neurotransmission in the developing brain is not known. Glutamatergic and GABAergic fluxes were assessed in neocortex of postnatal day 10 (P10) and 30 (P30) urethane-anesthetized rats infused intravenously with [1,6-13C2]glucose for different time intervals (time course) or with [2-13C]acetate for 2 to 3 h (steady state). Amino acid levels and 13C enrichments were determined in tissue extracts ex vivo using 1H-[13C]-NMR spectroscopy. Metabolic fluxes were estimated from the best fits of a three-compartment metabolic model (glutamatergic neurons, GABAergic neurons, and astroglia) to the 13C-enrichment time courses of amino acids from [1,6-13C2]glucose, constrained by the ratios of neurotransmitter cycling (Vcyc)-to-tricarboxylic acid (TCA) cycle flux (VTCAn) calculated from the steady-state [2-13C]acetate enrichment data. From P10 to P30 increases in total neuronal (glutamate plus GABA) TCA cycle flux (3 ; 0.240.05 versus 0.710.07 mol per g per min, Pmol per g per min, PVcyc(tot)) and neuronal TCA cycle flux (VTCAn(tot)) between P10 and P30 were 0.23 to 0.27 and 0.47 mol per g per min, respectively, similar to the 1:2 relationship previously reported for adult cortex. For the individual neurons, increases in VTCAn and Vcyc were similar in magnitude (glutamatergic neurons, 2.7 versus 2.8 to 4.6 ; GABAergic neurons, 5 versus 7 ), although GABAergic flux changes were larger. The findings show that glutamate and GABA neurons undergo large and approximately proportional increases in neurotransmitter cycling and oxidative energy metabolism during this major postnatal growth spurt.