Competition between glucose and lactate as oxidative energy substrates in both neurons and astrocytes: a comparative NMR study

Abstract

Competition between glucose and lactate as oxidative energy substrates was investigated in both primary cultures of astrocytes and neurons using physiological concentrations (1.1 mm for each). Glucose metabolism was distinguished from lactate metabolism by using alternatively labelled substrates in the medium ([1-13C]glucose + lactate or glucose + [3-13C]lactate). After 4 h of incubation, 1H and 13C-NMR spectra were realized on perchloric acid extracts of both cells and culture media. For astrocytic cultures, spectra showed that amino acids (glutamine and alanine) were more labelled in the glucose-labelled condition, indicating that glucose is a better substrate to support oxidative metabolism in these cells. The opposite was observed on spectra from neuronal cultures, glutamate being much more labelled in the lactate-labelled condition, confirming that neurons consume lactate preferentially as an oxidative energy substrate. Analysis of glutamine and glutamate peaks (singlets or multiplets) also suggests that astrocytes have a less active oxidative metabolism than neurons. In contrast, they exhibit a stronger glycolytic metabolism than neurons as indicated by their high lactate production yield. Using a mathematical model, we have estimated the relative contribution of exogenous glucose and lactate to neuronal oxidative metabolism. Under the aforementioned conditions, it represents 25% for glucose and 75% for lactate. Altogether, these results obtained on separate astrocytic and neuronal cultures support the idea that lactate, predominantly produced by astrocytes, is used as a supplementary fuel by neurons in vivo already under resting physiological conditions.

Nonenzymatic Proton Handling by Carbonic Anhydrase II during H+-Lactate Cotransport via Monocarboxylate Transporter 1

“…3D). Catalytic activity of CAI, as determined by the rate of rise in intracellular H ϩ concentration induced by application of 5% CO 2 , 10 mM HCO 3 Ϫ , was lower than the activity of CAII but still induced a significant increase in the rate of CO 2 -induced acidification and also showed a typical saturation curve (Fig. 3F).…”

“…The rate of rise in intracellular H ϩ concentration as induced by application of 5% CO 2 , 10 mM HCO 3 Ϫ showed a typical saturation curve (Fig. 3E).…”

“…Members of the MCT family, which belong to the human gene family SLC16 which comprise 14 isoforms, are expressed in most tissues, in particular those with a large energy consumption like muscle and brain (1,2). In the brain MCT1 is located mainly in glial cells, where it facilitates the export of lactate, which is then taken up by neurons via the high affinity MCT2; thereby the two isoforms are believed to shuttle lactate from glial cells to neurons which seems to be pivotal for brain energy metabolism (3)(4)(5)(6). In muscle, MCT1 is highly expressed in oxidative type I fibers, where it mediates import of lactate that is released by glycolytic muscle cells via MCT3 and MCT4 (7)(8)(9).…”

“…Many Na ϩ -dependent and Na ϩ -independent transport modes of metabolites (e.g. neurotransmitter substances) also transport H ϩ , OH Ϫ , or HCO 3 Ϫ as co-or counter-substrate. The energetic compounds lactate and pyruvate are primarily transported by monocarboxylate transporters (MCT) 2 in an electroneutral 1 proton-1 organic anion transport mode.…”

Prostaglandin transporter expression in mouse brain during development and in response to hypoxia

“…To date, evidence has accumulated that under normoxic conditions atrocytes and neurons have distinct metabolic preferences (McKenna et al, 1993;McKenna et al, 2001;Pellerin et al, 1998). Astrocytes consume glucose and generate large amounts of lactate, whereas neurons preferentially utilize lactate to support their oxidative metabolism (Bouzier-Sore et al, 2006;McKenna et al, 2001). Thus, the presence of PGT in neurons during normoxic baseline conditions is important not only for PG transport but also for metabolic and energy substrate trafficking.…”