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Neurotransmitters Regulate Energy Metabolism in Astrocytes: Implications for the Metabolic Trafficking between Neural Cells
Open accessAbstract
In recent years a vast array of experimental evidence has indicated the presence of functional receptors for neurotransmitters on nonneuronal cells, in particular astrocytes. The two neurotransmitters vasoactive intestinal peptide (VIP) and noradrenaline (NA) exert profound, receptor-mediated, metabolic actions on astrocytes. Thus both neurotransmitters stimulate glycogenolysis in primary astrocyte cultures, with EC50s of 3 and 20 nM respectively. Astrocytes display basal glucose utilization rates ranging between 3 and 9 nmol/mg prot/min, a value that is remarkably close to glucose utilization of cerebral cortical grey matter as determined by the 2-deoxyglucose autoradiographic technique. NA markedly enhances glucose uptake and phosphorylation by astrocytes, with an EC50 of 1 microM. The metabolic substrate that is released by astrocytes is predominantly lactate and not glucose. Since lactate can support neuronal activity and synaptic function in vitro, the possibility should be considered that glucose uptake by the brain parenchyma occurs predominantly into astrocytes which subsequently release lactate for the use of neurons.
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In the citing paper
“Astrocytes can indeed produce lactate from glucose (Hertz et al., 1988; Magistretti et al., 1993), and this lactate production can be stimulated by glutamate and potassium, which become elevated during neuronal activity (Walz and Mukerji, 1988; Peng et al., 1994; Pellerin and Magistretti, 1996; Bittner et al., 2011).”
From Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism (2018) · cites this paper as Magistretti et al., 1993
In the citing paper
“For instance, the initial demonstration of feasibility was from separately cultured astrocytes and neurons: glutamate application to cultured astrocytes triggers [3H]-2-deoxyglucose (2-DG; [3H]–2-DG) uptake and lactate release, and neurons are capable of consuming lactate as a fuel (Magistretti et al., 1993; Pellerin and Magistretti, 1994).”
From Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism (2018) · cites this paper as Magistretti et al., 1993
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Activity-dependent regulation of energy metabolism by astrocytes: an update
Pellerin, L., Bouzier‐Sore, A., Aubert, A., Serres, S., Merle, M., Costalat, R., & Magistretti, P. J. (2007) · Glia · doi:10.1002/glia.20528 · Cited by 805
“GLIA DOI 10.1002/glia”
BackgroundInfluentialSelf-citationBrain metabolism in health, aging, and neurodegeneration
Camandola, S., & Mattson, M. P. (2017) · The EMBO Journal · doi:10.15252/embj.201695810 · Cited by 752
“The reason why glycogen is produced and stored exclusively in astrocytes (Magistretti et al, 1993) is because in neurons GS is maintained in a constitutively inactive state by hyperphosphorylation via glycogen synthase kinase 3 (GSK3), and subsequent ubiquitin-dependent proteasomal The EMBO Journal…”
Monocarboxylate transporters in the central nervous system: distribution, regulation and function
Pierre, K., & Pellerin, L. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03168.x · Cited by 744
Self-citationWang, D. D., & Bordey, A. (2008) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2008.09.015 · Cited by 538
“…coupled receptors and ionotropic receptors that have been extensively reviewed (for review see Salm and McCarthy, 1992; Hosli and Hosli, 1993; Magistretti et al., 1993; Whitaker-Azmitia and Azmitia, 1994; Kimelberg, 1995; Vernadakis, 1996; Fraser et al., 1997; Porter and McCarthy, 1997;…”
BackgroundRole of Monocarboxylate Transporters in Drug Delivery to the Brain
Vijay, N., & Morris, M. (2014) · Current Pharmaceutical Design · doi:10.2174/13816128113199990462 · Cited by 408
Metadata
- Authors
- Magistretti, P. J., Sorg, O., Yu, N., Martin, J.-L., & Pellerin, L.
- Affiliations
- University of Lausanne (CH)
- Venue
- Developmental Neuroscience
- Publisher
- S. Karger AG
- Published
- 1994-08-18
- Volume
- 15
- Issue
- 3-5
- Pages
- 306-312
- ISSN
- 0378-5866 (ISSN-L)
- 1421-9859
- OpenAlex
- W2064182395
- Cited by
- 205
- References
- 0
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 6 · 2023: 1 · 2022: 5 · 2021: 7 · 2020: 5 · 2019: 6 · 2018: 8 · 2017: 10 · 2016: 5 · 2015: 7 · 2014: 10 · 2013: 6 · 2012: 10
- FWCI
- 1.03
- Type
- journal article
- Language
- en
- Open access
- green
- infoscience.epfl.ch
- Locations
- Developmental Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (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 › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- astrocytes, vasoactive intestinal peptide, norepinephrine, glycogenolysis, glucose uptake, glucose phosphorylation, lactate release, astrocyte-neuron metabolic coupling, energy metabolism, non-neuronal cells
- MeSH terms
- Animals, Astrocytes, Energy Metabolism, Glucose, Glycogen, Humans, Neurons, Norepinephrine, Vasoactive Intestinal Peptide, Neurotransmitter Agents
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