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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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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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