Partitioning of CO₂ Production Between Glucose and Lactate in Excised Sympathetic Ganglia, with Implications for Brain

Abstract

Chains of lumbar sympathetic ganglia from 15‐day‐old chicken embryos were incubated for 4 h at 36°C in a bicarbonate‐buffered salt solution equilibrated with 5% CO2‐95% O2. Glucose (1–10 mM), lactate (1–10 mM), [U‐14C]glucose, [1‐14C]glucose, [6‐14C]glucose, and [U‐14C]lactate were added as needed. 14CO2 output was measured continuously by counting the radioactivity in gas that had passed through the incubation chamber. Lactate reduced the output of CO2 from [U‐14C]glucose, and glucose reduced that from [U‐14C]lactate. When using uniformly labeled substrates in the presence of 5.5 mM glucose, the output of CO2 from lactate exceeded that from glucose when the lactate concentration was >2 mM. The combined outputs at each concentration tested were greater than those from either substrate alone. The 14CO2 output from [1‐14C]glucose always exceeded that from [6‐14C]glucose, indicating activity of the hexose monophosphate shunt. Lactate reduced both of these outputs, with the maximum difference between them during incubation remaining constant as the lactate concentration was increased, suggesting that lactate may not affect the shunt. Modeling revealed many details of lactate metabolism as a function of its concentration. Addition of a blood‐brain barrier to the model suggested that lactate can be a significant metabolite for brain during hyperlactemia, especially at the high levels reached physiologically during exercise.

Lactate is a Preferential Oxidative Energy Substrate over Glucose for Neurons in Culture

“…Thus, on this basis, it can be argued that lactate might represent a better oxidative substrate than glucose for neurons, at least in vitro. This conclusion is consistent with numerous other studies performed by measuring CO 2 production on synaptic terminals (McKenna et al, 1993(McKenna et al, , 1994(McKenna et al, , 1998, excised sympathetic ganglia (Larrabee, 1996), brain slices (Fernandez and Medina, 1986;Ide et al, 1969), and cultured neurons (McKenna et al, 2001;Tabernero et al, 1996;Vicario et al, 1991), all of which have shown preferential oxidation of lactate over glucose.…”

Effects of sciatic nerve transection on glucose uptake in the presence and absence of lactate in the frog dorsal root ganglia and spinal cord

“…The use of lactate as an energy substrate by the frog DRG also concords with observations from studies of mammals and non-mammals. Previous studies showed a preferential use for lactate in avian, mammalian and human neuronal oxidative metabolism (Larrabee, 1980(Larrabee, , 1996BouzierSore et al, 2003BouzierSore et al, , 2006Pellerin and Magistretti, 2012).…”

“…The tissues were incubated with 0.15 µCi of 14 C-2-DG plus 10 mM lactate for 60 min under the same conditions initially described. This value was chosen for lactate because it was used in other studies with the ganglion (Larrabee, 1980(Larrabee, , 1996.…”

Dual-Gene, Dual-Cell Type Therapy against an Excitotoxic Insult by Bolstering Neuroenergetics

“…Lactate can be used as an oxidative substrate in brain slices (Ide et al, 1969;Fernandez and Medina, 1986), cultured telencephalic neurons (Tabernero et al, 1996;McKenna et al, 2001), aggregated neuronal cultures (Honegger et al, 2002), sympathetic ganglia (Larrabee, 1996), and synaptic terminals (McKenna et al, 1993) and can be preferred to glucose (Bouzier-Sore et al, 2003;Itoh et al, 2003;Smith et al, 2003). In addition, metabolic demands increase neuronal ability to use lactate (Schurr et al, 1999).…”