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Glutamate triggers rapid glucose transport stimulation in astrocytes as evidenced by real-time confocal microscopy.
Open accessAbstract
Glutamate stimulates glycolysis in astrocytes, a phenomenon that couples astrocytic metabolism with neuronal activity. However, it is not known whether glutamate also affects glucose transporter-1 (GLUT1), the transporter responsible for glucose entry into astrocytes. To address this question, two different real-time single-cell hexose uptake assays were applied to cultured hippocampal astrocytes using confocal epifluorescence microscopy. Glutamate caused a twofold to threefold increase in the zero-trans uptake rates of the fluorescent hexoses 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose (2-NBDG) and 6-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-6-deoxyglucose (6-NBDG). Galactose uptake, determined by the calcein volumetric assay, was stimulated to a similar extent, confirming the fluorescent hexose data, and also demonstrating that glutamate stimulation is a Vmax effect. Remarkably, glucose transport stimulation developed fully inside 10 sec, which is 100 times faster than acute stimulations of glucose transport in other cell types. Glutamate did not significantly affect the rate of 6-NBDG uptake by GLUT1-expressing epithelial Clone 9 cells, suggesting that an astrocyte-specific factor is required for transport stimulation. We conclude that glucose transport stimulation occurs early during astrocytic activation by glutamate, which provides a novel regulatory node to current models of brain energy metabolism. This mechanism should also be considered for the interpretation of functional imaging data based on hexoses.
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“As a consequence, the total glucose use by neurons and astrocytes together is coupled directly to glutamate-mediated synaptic transmission [32], [34], [36], which accounts for 80–90% of total glucose use in the cerebral cortex [32].”
From Scaling of Brain Metabolism with a Fixed Energy Budget per Neuron: Implications for Neuronal Activity, Plasticity and Evolution (2011) · cites this paper as [36]
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Metadata
- Authors
- Loaiza, A., Porras, O. H., & Barros, L. F.
- Affiliations
- Centro de Estudios Científicos (CL)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2003-08-13
- Volume
- 23
- Issue
- 19
- Pages
- 7337-7342
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6740433
- OpenAlex
- W2119476349
- Cited by
- 254
- References
- 34
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 6 · 2023: 11 · 2022: 11 · 2021: 10 · 2020: 10 · 2019: 15 · 2018: 8 · 2017: 14 · 2016: 13 · 2015: 10 · 2014: 13 · 2013: 13 · 2012: 9
- FWCI
- 3.24
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- 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, GLUT1, astrocytes, astrocyte-neuron interaction, glycolysis, hippocampal astrocytes, 2-NBDG, galactose uptake, brain energy metabolism, astrocyte activation
- MeSH terms
- Animals, Astrocytes, Biological Transport, Deoxyglucose, Fluorescent Dyes, Glucosamine, Glucose, Hippocampus, Kinetics, 4-Chloro-7-nitrobenzofurazan, Neurons, Rats, Sprague-Dawley, Microscopy, Confocal, Glutamic Acid, Coculture Techniques, Rats
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