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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Astrocytes can produce lactate from glucose.
“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 separately cultured astrocytes and neurons, glutamate application to cultured astrocytes triggers [3H]-2-deoxyglucose uptake and lactate release, and neurons are capable of consuming lactate as a fuel.
“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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“Since astrocytes have relatively high energy demands compared to neurons .Leo et al., 1993; Magistretti et al., 1993 , activated glial cells may require even higher glucose utilization, which would be associated with increased rCBF due to the tight coupling of cerebral glucose consumption and blood flow Raichle, . 198…”
BackgroundBrain lactate uptake increases at the site of impact after traumatic brain injury
Chen, T., Qian, Y. Z., Rice, A. C., Zhu, J., Di, X., & Bullock, R. M. (2000) · Brain Research · doi:10.1016/s0006-8993(00)01992-2 · Cited by 63 · see citing works
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Impaired CO 2 sensitivity of astrocytes in a mouse model of Rett syndrome
Turovsky, E. A., Karagiannis, A., Abdala, A. P., & Gourine, A. V. (2015) · The Journal of Physiology · doi:10.1113/jp270369 · Cited by 62 · see citing works
“The astrocyte–neurone lactate shuttle hypothesis proposes that astrocytes support neuronal activity by supplying neuronal networks with metabolic substrate in the form of lactate (Magistretti et al. 1993, 1994; Pellerin & Magistretti, 1994).”
BackgroundA New Outlook on Mental Illnesses: Glial Involvement Beyond the Glue
Elsayed, M., & Magistretti, P. J. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00468 · Cited by 59 · see citing works
“It is well known that catecholamines can trigger glycogenolysis in astrocytes followed by lactate release (Magistretti, 1988; Sorg and Magistretti, 1991; Magistretti et al., 1993).”
BackgroundSelf-citationNeuron–astrocyte interactions in neurodegenerative diseases: Role of neuroinflammation
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“Extensive experimental work has characterized the importance of - and -adrenergic receptors within the central nervous system influencing cerebral glucose metabolism (31, 32), cerebral perfusion (33–35), neuronal activity, and cerebral oxygen consumption (9–11).”
BackgroundNoradrenergic Regulation of Glial Activation: Molecular Mechanisms and Therapeutic Implications
Braun, D. J., Madrigal, J. L. M., & Feinstein, D. L. (2014) · Current Neuropharmacology · doi:10.2174/1570159x12666140828220938 · Cited by 56 · see citing works
“Glycogen metabolism is also greatly increased by stimulation of β-ARs [8, 9].”
BackgroundDisturbance of aerobic metabolism accompanies neurobehavioral changes induced by nickel in mice
He, M., Xu, S., Zhang, X., Wang, Y., Xiong, J., Zhang, X., Lu, Y., Zhang, L., Yu, Z., & Zhou, Z. (2013) · NeuroToxicology · doi:10.1016/j.neuro.2013.05.011 · Cited by 57 · see citing works
Pierre, K., Debernardi, R., Magistretti, P. J., & Pellerin, L. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.01964.x · Cited by 57 · see citing works
“Indeed, it was shown to enhance both glycogenolysis and glycolysis in brain slices and cultured astrocytes (Magistretti et al. 1993; Tsacopoulos and Magist- retti 1996).”
BackgroundSelf-citationLactate spares glucose as a metabolic fuel in neurons and astrocytes from primary culture
Tabernero, A., Vicario, C., & Medina, J. M. (1996) · Neuroscience Research · doi:10.1016/s0168-0102(96)01121-2 · Cited by 57 · see citing works
“Moreover, some evidence suggests that lactate plays a role in the traffic of metabolites between neurons and astrocytes (Magistretti et al., 1993; Poitry Yamate et al., 1995; Sonnewald et al., 1995).”
BackgroundAstrocytes as the Glucose Shunt for Glutamatergic Neurons at High Activity: An In Silico Study
Occhipinti, R., Somersalo, E., & Daniela Calvetti, A. (2008) · Journal of Neurophysiology · doi:10.1152/jn.90377.2008 · Cited by 57 · see citing works
Ryabinin, A. E., & Wang, Y. (1998) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.1998.tb03962.x · Cited by 56 · see citing works
CNS sensing and regulation of peripheral glucose levels
Levin, B. E., Dunn-Meynell, A. A., & Routh, V. H. (2002) · International review of neurobiology · doi:10.1016/s0074-7742(02)51007-2 · Cited by 54 · see citing works
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Ca2+ signals of astrocytes are modulated by the NAD+/NADH redox state
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The Monoaminergic Tripartite Synapse: A Putative Target for Currently Available Antidepressant Drugs
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“Given that astrocytes are the main cerebral source of glycogen and that the glycogenogenesis and glycogenolysis are key processes for the rapid production of energetic substrates [106-109], it is likely that the stimulation of the astrocytic 1- and 2-adrenoceptors plays a major role in the metabolism necessary for the…”
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“We predicted that NE would stimulate VMN GP protein expression in vivo as this neurochemical is reported to enhance cerebral astrocyte glycogenolysis in vitro [Harik et al., 1982; Magistretti et al., 1993]; however, current data instead show a Cc-preventable reduction in GS and GP profiles in NE-treated animals at +2…”
BackgroundAstrocyte Mitochondria in In Vitro Models of Ischemia
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“…homeostasis, including several energy-dependent functions necessary for normal neuronal activity, e.g., regulation of extracellular K+, pH, and osmolality; export of metabolic intermediates; and rapid uptake of neurotransmitters (Kimelberg and Norenberg, 1989; Magistretti et al., 1993; Walz, 2000).”
BackgroundHistamine and astrocyte function
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Improving the survival of human CNS precursor‐derived neurons after transplantation
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“…that astrocytic glycogen can act as an energy store for astrocytes themselves or for neighboring neurons, oligodendrocytes, and microglia by releasing glycogen-derived lactate that can then be metabolized by other cells (Dringen et al., 1993; Magistretti et al., 1993; Pellerin et al., 1997).”
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Differences in Activity of Cytochrome C Oxidase in Brain Between Sleep and Wakefulness
Nikonova, E. V., Vijayasarathy, C., Zhang, L., Cater, J. R., Galante, R. J., Ward, S. E., Avadhani, N. G., & Pack, A. I. (2005) · SLEEP · doi:10.1093/sleep/28.1.21 · Cited by 49 · see citing works
Wan, H., Hulsey, M. G., & Martin, R. J. (1998) · Journal of Nutrition · doi:10.1093/jn/128.2.287 · Cited by 49 · see citing works
- 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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