Neuronal glucose but not lactate utilization is positively correlated with NMDA‐induced neurotransmission and fluctuations in cytosolic Ca2+levels
Abstract
Although the brain utilizes glucose for energy production, individual brain cells may to some extent utilize substrates derived from glucose. Thus, it has been suggested that neurons consume extracellular lactate during synaptic activity. However, the precise role of lactate for fueling neuronal activity is still poorly understood. Recently, we demonstrated that glucose metabolism is up-regulated in cultured glutamatergic neurons during neurotransmission whereas that of lactate is not. Here, we show that utilization of glucose but not lactate correlates with NMDA-induced neurotransmitter glutamate release in cultured cerebellar neurons from mice. Pulses of NMDA at 30, 100, and 300 microM, leading to a progressive increase in both cytosolic [Ca2+] and release of glutamate, increased uptake and metabolism of glucose but not that of lactate as evidenced by mass spectrometric measurement of 13C incorporation into intracellular glutamate. In this manuscript, a cascade of events for the preferential neuronal utilization of glucose during neurotransmission is suggested and discussed in relation to our current understanding of neuronal energy metabolism.
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In cultured neurons, graded NMDA stimulation producing moderate submicromolar increases in cytosolic calcium increased glucose metabolism over twofold, whereas lactate metabolism declined.
“Similar experiments using graded neuronal stimulation by NMDA, which produced moderate submicromolar increases in cytosolic calcium, showed that activation increased glucose metabolism over twofold, whereas lactate metabolism declined, consistent with a role for extracellular lactate supporting basal metabolism in neurons but not stimulated activity (Bak et al., 2009).”
From Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism (2018) · cites this paper as Bak et al., 2009
Extracellular lactate supports basal metabolism in neurons but not stimulated activity.
“Similar experiments using graded neuronal stimulation by NMDA, which produced moderate submicromolar increases in cytosolic calcium, showed that activation increased glucose metabolism over twofold, whereas lactate metabolism declined, consistent with a role for extracellular lactate supporting basal metabolism in neurons but not stimulated activity (Bak et al., 2009).”
From Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism (2018) · cites this paper as Bak et al., 2009
Neurons can metabolize glucose.
“Neurons express all of the enzymes needed for glucose metabolism (Fig. 1) and can metabolize glucose (Bak et al., 2009).”
From Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism (2018) · cites this paper as Bak et al., 2009
Direct neuronal glycolysis is recruited in response to stimulation in a relatively intact system.
“The inferred recruitment of direct neuronal glycolysis in response to stimulation in a relatively intact system is consistent with earlier carbon tracing studies on cultured neurons (Bak et al., 2009, 2012).”
From Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism (2018) · cites this paper as Bak et al., 2009
Moderate chemical stimulation produced a strong increase in labeling of glutamate from labeled glucose and a decrease in incorporation of label from labeled lactate, inconsistent with significant lactate utilization by neurons during stimulation.
“Moderate chemical stimulation produced a strong increase in the labeling of glutamate from labeled glucose and a decrease in the incorporation of label from labeled lactate, inconsistent with significant lactate utilization by neurons during stimulation.”
From Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism (2018) · cites this paper as Bak et al., 2009
In cultured neurons, unlabeled lactate does not diminish the increased utilization of labeled glucose with stimulation, but it does reduce labeling from glucose at rest.
“Furthermore, although in cultured neurons, unlabeled lactate does not diminish the increased utilization of labeled glucose with stimulation, it does reduce labeling from glucose at rest (Bak et al., 2009).”
From Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism (2018) · cites this paper as Bak et al., 2009
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References 29 · Cited by 107
- Authors
- Bak, L. K., Walls, A. B., Schousboe, A., Ring, A., Sonnewald, U., & Waagepetersen, H. S.
- Affiliations
- University of Copenhagen (DK)
- Norwegian Defence Research Establishment (NO)
- Norwegian University of Science and Technology (NO)
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2009-04-07
- Volume
- 109
- Issue
- s1
- Pages
- 87-93
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W1968678510
- Cited by
- 107
- References
- 29
- Citations by year
- 2025: 5 · 2024: 8 · 2023: 5 · 2022: 8 · 2021: 18 · 2020: 3 · 2019: 7 · 2018: 8 · 2017: 2 · 2016: 5 · 2015: 5 · 2014: 3 · 2013: 9 · 2012: 10
- FWCI
- 2.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- lactate utilization, NMDA receptor, glutamate release, neurotransmission, intracellular calcium, cerebellar neurons, neuronal energy metabolism, 13C labeling, glutamate uptake
- MeSH terms
- Animals, Antimetabolites, Aspartic Acid, Calcium, Cells, Cultured, Cerebellum, Cytosol, Deoxyglucose, Glucose, Malates, Synaptic Transmission, Neurons, N-Methylaspartate, Neurotransmitter Agents, Excitatory Amino Acid Agonists, Lactic Acid, Calcium Signaling, Mice
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