ELSEVIER Neuroscience Research 26 (1996) 369-376 NEUROSCIENCE RESEARCH Lactate spares glucose as a metabolic fuel in neurons and astrocytes from primary culture A. Tabernero, C. Vicario, J.M. Medina* Departamento de Bioquimica y Biologla Molecular, Edificio Departamental, Facultad de Farmacia, Universidad de Salamanca, Ada Campo Charro s /n., E-37080 Salamanca, Spain Received 25 July 1996; accepted 7 October 1996 Abstract The effect of lactate on glucose metabolism in neurons and astrocytes from primary culture has been studied. The rates of glucose metabolism through the pentose-phosphate shunt, the pyruvate dehydrogenase-catalyzed reaction, the tricarboxylic acid cycle, the total lipogenesis and the synthesis of glycerol-borne lipids in astrocytes were 2-3 fold higher than in neurons. However, the rate of glucose incorporation into sterols and esterified fatty acids was similar in both types of cells. Total glucose utilization was inhibited by lactate to the same extend in both neurons and astrocytes. Lactate strongly inhibited glucose oxidation through the pyruvate dehydrogenase-catalyzed reaction and the tricarboxylic acid cycle, in both neurons (60 and 44%, respectively) and astrocytes (64 and 62%, respectively). Glucose incorporation into sterols and fatty acids was also inhibited by lactate in both neurons and astrocytes (57 and 76%, respectively) while the oxidation of glucose in the pentose-phosphate shunt and the synthesis of glycerol-borne lipids was not significantly affected. These results suggest that in the presence of lactate both neurons and astrocytes can utilize lactate as the major metabolic substrate, sparing glucose for the synthesis of NADPH(H +), ribose-5-phos- phate and/or glycerol-borne lipids. An interaction between glucose and lactate metabolism at the level of the pyruvate dehydrogenase-catalyzed reaction is suggested. Copyright © 1996 Elsevier Science Ireland Ltd Keywords: Brain; Metabolism; Hypoglycaemia; Hyperlactiacidemia 1. Introduction Immediately after delivery, the rate of liver glycogenolysis is very low (Cuezva et al., 1980; Fernan- dez et al., 1983; Girard et al., 1973) and the gluconeo- genic capacity of the liver is negligible (Fernandez et al., 1983; Medina et al., 1980), resulting in very low plasma concentrations of glucose (Cuezva et al., 1980; Girard et al., 1973). However, lactate accumulates in the blood during late gestation, reaching concentrations higher than 9 mM during the first minutes of extrauterine life Abbreviations: PBS, phosphate-buffered saline; BSA, fatty acid-free bovine serum albumin; DMEM, Dulbecco's modified Eagle's medium; FCS, fetal calf serum; EBS, Earle's balanced solution; GFAP, glial fibrillary acidic protein. *Corresponding author. Fax: +34 23 294564; e-mail: med- ina@gugu.usal.es (Cuezva et al., 1980; Juanes et al., 1986). In addition a number of observations are consistent with the hypoth- esis that lactate is an important metabolic substrate for the brain during the early neonatal period (for a review see, Medina et al., 1992). Moreover, some evidence suggests that lactate plays a role in the traffic of metabolites between neurons and astrocytes (Magistretti et al., 1993; Poitry Yamate et al., 1995; Sonnewald et al., 1995). In this context, glycogen, the major brain energy reserve, is located mainly in astro- cytes (Cataldo and Broadwell, 1986) but is responsible for neuronal survival under glucose deprivation (Swan- son and Choi, 1993). However, glycogen is released by astrocytes as lactate (Dringen et al., 1993a) which is presumably used by neurons as a source of energy and carbon skeletons (Tabernero et al., 1993; Vicario et al., 1993). In addition, lactate may be piped through astro- 0168-0102/96/$15.00 Copyright © 1996 Elsevier Science Ireland Ltd. All rights reserved PII SO 168-01 02(96)01 12 1-2