Ex vivo NMR study of lactate metabolism in rat brain under various depressed states

Abstract

Brain endogenous lactate metabolism was investigated by ex vivo nuclear magnetic resonance (NMR) spectroscopy study after the infusion of rats with a solution of glucose and lactate labeled as either [3-(13)C]lactate or [1-(13)C]glucose, when their cerebral activity was more or less depressed under the influence of either pentobarbital, alphachloralose, or morphine. We found that: (1) the ratio between the enrichment of alanine C3 and that of glutamate C4, gamma-aminobutyric acid (GABA) C2, glutamine C4, or aspartate C3 decreased from pentobarbital to alphachloralose and morphine whatever the labeled precursor, indicating a link between metabolic and cerebral activity; (2) under glucose + [3-(13)C]lactate infusion, alanine C3 and acetyl-CoA C2 enrichments were higher than that of lactate C3, revealing the occurrence of an isotopic dilution of the brain exogenous lactate (arising from the blood) by lactate from the brain (endogenous lactate), and that the latter was synthesized from glycolysis in a compartment other than neurons; and (3) the contribution of labeled glucose and lactate to acetyl-CoA and amino acid enrichment indicated that the involvement of blood glucose relative to that of blood lactate to brain metabolism was correlated with cerebral activity. The evolution of metabolite enrichments, however, indicated that the cerebral activity-dependent increase in the contribution of blood glucose relative to that of blood lactate to brain metabolism occurred partly via the increase in lactate metabolism generated from astrocytic glycolysis. These findings support the hypothesis for an astrocyte-neuron lactate shuttle component in the coupling mechanism between cerebral activity and energy metabolism.