COMPARISON OF LACTATE AND GLUCOSE-METABOLISM IN CULTURED NEOCORTICAL NEURONS AND ASTROCYTES USING C-13-NMR SPECTROSCOPY

In cerebral cortical neurons, synthesis of the tricarboxylic acid (TCA ) cycle-derived amino acids, glutamate and aspartate as well as the ne urotransmitter of these neurons, gamma-aminobutyrate (GABA), was studi ed incubating the cells in media containing 0.5 mM [U-C-13]glucose in the absence or presence of glutamine (0.5 mM), Lyophilized cell extrac ts were analyzed by C-13 nuclear magnetic resonance (NMR) spectroscopy and HPLC. The present findings were compared to results previously ob tained using 1.0 mM [U-C-13]lactate as the labeled substrate for the n eurons. Regardless of the amino acids studied, incubation periods of 1 and 4 h resulted in identical amounts of C-13 incorporated. Furthermo re, the metabolism of lactate was studied under analogous conditions i n cultured cerebral cortical astrocytes, The incorporation of C-13 fro m lactate into glutamate was much lower in the astrocytes than in the neurons. In cerebral cortical neurons the total amount of C-13 in GABA , glutamate and aspartate was independent of the labeled substrate. Th e enrichment in glutamate and aspartate was, however, higher in neuron s incubated with lactate. Thus, lactate appears to be equivalent to gl ucose with regard to its access to the TCA cycle and subsequent labeli ng of glutamate, aspartate and GABA, It should be noted, however, that incubation with lactate in place of glucose led to lower cellular con tents of glutamate and aspartate, The presence of glutamine affected t he metabolism of glucose and lactate differently, suggesting that the metabolism of these substrates may be compartmentalized.