Glutamate mediates acute glucose transport inhibition in hippocampal neurons
Open accessAbstract
Although it is known that brain activity is fueled by glucose, the identity of the cell type that preferentially metabolizes the sugar remains elusive. To address this question, glucose uptake was studied simultaneously in cultured hippocampal neurons and neighboring astrocytes using a real-time assay based on confocal epifluorescence microscopy and fluorescent glucose analogs. Glutamate, although stimulating glucose transport in astrocytes, strongly inhibited glucose transport in neurons, producing in few seconds a 12-fold increase in the ratio of astrocytic-to-neuronal uptake rate. Neuronal transport inhibition was reversible on removal of the neurotransmitter and displayed an IC50 of 5 microm, suggesting its occurrence at physiological glutamate concentrations. The phenomenon was abolished by CNQX and mimicked by AMPA, demonstrating a role for the cognate subset of ionotropic glutamate receptors. Transport inhibition required extracellular sodium and calcium and was mimicked by veratridine but not by membrane depolarization with high K+ or by calcium overloading with ionomycin. Therefore, glutamate inhibits glucose transport via AMPA receptor-mediated sodium entry, whereas calcium entry plays a permissive role. This phenomenon suggests that glutamate redistributes glucose toward astrocytes and away from neurons and represents a novel molecular mechanism that may be important for functional imaging of the brain using positron emission tomography.
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The glucose dips do not result from an activity-induced decrease in glucose transport.
“This argues that the two effects are mechanistically connected, and thus it argues against the idea that the glucose dips result from a reported activity-induced decrease in glucose transport (Porras et al., 2004).”
From Neuronal Stimulation Triggers Neuronal Glycolysis and Not Lactate Uptake (2017) · cites this paper as Porras et al., 2004
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- Authors
- Porras, O. H., Loaiza, A., & Barros, L. F.
- Affiliations
- Centro de Estudios Científicos (CL)
- Corresponding author
- Barros, L. Felipe
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2004-10-27
- Volume
- 24
- Issue
- 43
- Pages
- 9669-9673
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6730152
- OpenAlex
- W2037140288
- Cited by
- 139
- References
- 31
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 3 · 2021: 2 · 2020: 3 · 2019: 4 · 2018: 9 · 2017: 10 · 2016: 5 · 2015: 7 · 2014: 9 · 2013: 11 · 2012: 7
- FWCI
- 2.81
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Americanae (AECID Library) (submittedVersion, other-oa)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- Funders
- Tinker Foundation
- 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 › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- glutamate, glucose transport, hippocampal neurons, astrocytes, AMPA receptors, ionotropic glutamate receptors, sodium entry, calcium influx, glucose metabolism, brain energy metabolism, CNQX, veratridine
- MeSH terms
- Animals, Astrocytes, Biological Transport, Cells, Cultured, Deoxyglucose, Fluorescent Dyes, Glucosamine, Glucose, Hippocampus, Monosaccharide Transport Proteins, 4-Chloro-7-nitrobenzofurazan, Neurons, Calcium Channels, Sodium Channels, Rats, Sprague-Dawley, Receptors, AMPA, alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid, Glutamic Acid, 6-Cyano-7-nitroquinoxaline-2,3-dione, Rats
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