The DOI matches its Crossref record; 66 of the 67 references it cites were found in a registry or an index.
Do active cerebral neurons really use lactate rather than glucose?
Abstract
Glucose has long been considered the substrate for neuronal energy metabolism in the brain. Recently, an alternative explanation of energy metabolism in the active brain, the astrocyte-neuron lactate shuttle hypothesis, has received attention. It suggests that during neural activity energy needs in glia are met by anaerobic glycolysis, whereas neuronal metabolism is fueled by lactate released from glia. In this article, we critically examine the evidence supporting this hypothesis and explain, from the perspective of enzyme kinetics and substrate availability, why neurons probably use ambient glucose, and not glial-derived lactate, as the major substrate during activity.
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“The ANLS hypothesis has been quite controversial for a long time (Chih et al., 2001; Gjedde and Marrett, 2001; Hertz, 2004; Mangia et al., 2011; Dienel, 2012, 2017; Bak and Walls, 2018; Barros and Weber, 2018; see also Dienel [2017] for strong arguments against ANLS at the tissue level).”
From Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism (2018) · cites this paper as Chih et al., 2001
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Cites
Pellerin, L., & Magistretti, P. J. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.22.10625 · Cited by 2,927
Magistretti, P. J., Pellerin, L., Rothman, D. L., & Shulman, R. G. (1999) · Science · doi:10.1126/science.283.5401.496 · Cited by 1,170
Malonek, D., & Grinvald, A. (1996) · Science · doi:10.1126/science.272.5261.551 · Cited by 1,109
Nature and Development of Lactic Dehydrogenases
Cahn, R. D., Zwilling, E., Kaplan, N. O., & Levine, L. (1962) · Science · doi:10.1126/science.136.3520.962 · Cited by 943
Stoichiometric coupling of brain glucose metabolism and glutamatergic neuronal activity.
Sibson, N. R., Dhankhar, A., Mason, G. F., Rothman, D. L., Behar, K. L., & Shulman, R. G. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.1.316 · Cited by 897
Biochemistry and the central nervous system
MCILWAIN, H. (1986) · International Journal of Biochemistry · doi:10.1016/0020-711x(86)90172-2 · Cited by 781
Evidence Supporting the Existence of an Activity-Dependent Astrocyte-Neuron Lactate Shuttle
Pellerin, L., Pellegri, G., Bittar, P. G., Charnay, Y., Bouras, C., Martin, J., Stella, N., & Magistretti, P. J. (1998) · Developmental Neuroscience · doi:10.1159/000017324 · Cited by 757
Cellular mechanisms of brain energy metabolism and their relevance to functional brain imaging
Magistretti, P. J., & Pellerin, L. (1999) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.1999.0471 · Cited by 750
Lactate rise detected by 1H NMR in human visual cortex during physiologic stimulation.
Prichard, J. W., Rothman, D. L., Novotny, E. J., Petroff, O. A. C., Kuwabara, T., Avison, M. J., Howseman, A., Hanstock, C. C., & Shulman, R. G. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.13.5829 · Cited by 612
Lactate-supported synaptic function in the rat hippocampal slice preparation.
Schurr, A., West, C. A., & Rigor, B. (1988) · Science · doi:10.1126/science.3375817 · Cited by 594
Research works printed but not linked: 2
- Vannucci, 1997, Glucose transporter proteins in brain: delivery of glucose to neurons and glia, Glia, 21, 2, 10.1002/(SICI)1098-1136(199709)21:1<2::AID-GLIA2>3.0.CO;2-C · DOI · Paper page
- Wang, 1994, Glutamate-induced intracellular acidification of cultured hippocampal neurons, J. Physiol. (London), 354, 163
Cited by
Sorted by citations
Lactate metabolism: a new paradigm for the third millennium
Gladden, L. B. (2004) · The Journal of Physiology · doi:10.1113/jphysiol.2003.058701 · Cited by 1,332
“The conventional view is that neuronal energy metabolism is fuelled by glucose oxidation (Chih et al. 2001).”
BackgroundInfluentialNew roles for astrocytes: redefining the functional architecture of the brain.
Nedergaard, M., Ransom, B., & Goldman, S. A. (2003) · Trends in Neurosciences · doi:10.1016/j.tins.2003.08.008 · Cited by 1,334
The neural basis of functional brain imaging signals
Attwell, D., & Iadecola, C. (2002) · Trends in Neurosciences · doi:10.1016/s0166-2236(02)02264-6 · Cited by 957
Brain Glucose Metabolism: Integration of Energetics with Function
Dienel, G. A. (2018) · Physiological Reviews · doi:10.1152/physrev.00062.2017 · Cited by 911
The tripartite synapse: roles for gliotransmission in health and disease
Halassa, M. M., Fellin, T., & Haydon, P. G. (2007) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2006.12.005 · Cited by 852
Metadata
- Authors
- Chih, C.-P., Lipton, P., & Roberts, E. L.
- Affiliations
- Miami VA Healthcare System (US)
- University of Wisconsin–Madison (US)
- University of Miami (US)
- Corresponding author
- Roberts, Eugene L
- Venue
- Trends in Neurosciences
- Publisher
- Elsevier BV
- Published
- 2001-10
- Volume
- 24
- Issue
- 10
- Pages
- 573-578
- ISSN
- 0166-2236 (ISSN-L)
- OpenAlex
- W1966886729
- Cited by
- 252
- References
- 67
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2023: 3 · 2022: 6 · 2021: 3 · 2020: 8 · 2019: 5 · 2018: 6 · 2017: 12 · 2016: 3 · 2015: 6 · 2014: 8 · 2013: 5 · 2012: 13
- FWCI
- 1.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Trends in Neurosciences (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- astrocyte-neuron lactate shuttle, neuronal energy metabolism, glucose utilization, lactate, anaerobic glycolysis, brain energy metabolism, substrate availability, enzyme kinetics
- MeSH terms
- Animals, Astrocytes, Cerebral Cortex, Glucose, Humans, Neurons, Lactic Acid
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