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Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization.
Open accessAbstract
Glutamate, released at a majority of excitatory synapses in the central nervous system, depolarizes neurons by acting at specific receptors. Its action is terminated by removal from the synaptic cleft mostly via Na(+)-dependent uptake systems located on both neurons and astrocytes. Here we report that glutamate, in addition to its receptor-mediated actions on neuronal excitability, stimulates glycolysis--i.e., glucose utilization and lactate production--in astrocytes. This metabolic action is mediated by activation of a Na(+)-dependent uptake system and not by interaction with receptors. The mechanism involves the Na+/K(+)-ATPase, which is activated by an increase in the intracellular concentration of Na+ cotransported with glutamate by the electrogenic uptake system. Thus, when glutamate is released from active synapses and taken up by astrocytes, the newly identified signaling pathway described here would provide a simple and direct mechanism to tightly couple neuronal activity to glucose utilization. In addition, glutamate-stimulated glycolysis is consistent with data obtained from functional brain imaging studies indicating local nonoxidative glucose utilization during physiological activation.
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“Astrocytes are essential CNS cells for glucose uptake (Pellerin and Magistretti 1994; Pellerin 2018).”
From LDL Cholesterol Modulates Astrocyte Metabolism, Lipid Handling, and Morphology: Evidence From In Vitro and In Vivo Models (2026) · cites this paper as Pellerin and Magistretti 1994
Experimental — accuracy not yet measuredIn the citing paper
“Lactate taken up by neurons is reconverted into pyruvate and ultimately utilized by mitochondria to generate ATP.”
From Energy paradox in REM sleep: balancing supply and consumption in brain metabolism (2026) · cites this paper as [12]
In the citing paper
“Lactate produced in astrocytes can be released into the extracellular space via monocarboxylate transporters (MCTs). This lactate is subsequently taken up by neurons through neuronal MCTs, a process known as the astrocyte–neuron lactate shuttle (ANLS)12,13.”
From Energy paradox in REM sleep: balancing supply and consumption in brain metabolism (2026) · cites this paper as [12]
In the citing paper
“This may distinguish oligodendrocytes from astrocytes that express LDH and reportedly use a”
From Downregulated expression of lactate dehydrogenase in adult oligodendrocytes and its implication for the transfer of glycolysis products to axons (2024) · cites this paper as Pellerin & Magistretti, 1994
In the citing paper
“the calculation of the average metabolic cost per neuron defined here as the total metabolic cost of a structure divided by its number of neurons is justified by the finding that neurons and astrocytes are metabolically coupled [30].”
From Scaling of Brain Metabolism with a Fixed Energy Budget per Neuron: Implications for Neuronal Activity, Plasticity and Evolution (2011) · cites this paper as [30]
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Metabolic signature in nucleus accumbens for anti-depressant-like effects of acetyl-L-carnitine
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“Astrocytic function is fundamental in the resilience to stress and regulation of extrasynaptic glutamate homeostasis (Pellerin and Magistretti, 1994; Nasca et al., 2017).”
BackgroundPhysiology of Astroglial Excitability
Verkhratsky, A., Semyanov, A. V., & Zorec, R. (2020) · Function · doi:10.1093/function/zqaa016 · Cited by 68
“Increases in NKA transport, which accompany neuronal activity (to buffer Kþ or to expel excessive Naþ entering the cell in the course of glutamate uptake) are also linked to astroglial L-lactate production and hence are central for the operation of astrocyte-to-neurone-lactate shuttle (ANLS).(45) Operation of astrogli…”
BackgroundMetabolic Control of Epilepsy: A Promising Therapeutic Target for Epilepsy
Fei, Y., Shi, R., Song, Z. Q., & Wu, J. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.592514 · Cited by 68
“Lactate in the brain acts as an energy substrate through the ANLS (discussed in section Metabolic Features in the Brain).”
BackgroundInfluentialNeuroprotection and Disease Modification by Astrocytes and Microglia in Parkinson Disease
Takahashi, S., & Mashima, K. (2022) · Antioxidants · doi:10.3390/antiox11010170 · Cited by 73
“The involvement of astrocytes in neuronal energy metabolism has attracted much attention since it was first proposed by Pellerin and Magistretti in 1994 [49], and has been confirmed by several researchers [50–53].”
BackgroundCalì, C., Cantando, I., Veloz Castillo, M. F., Gonzalez, L., & Bezzi, P. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25168922 · Cited by 66
Roles of Glutamine Synthetase Inhibition in Epilepsy
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“glycolytic ATP formation needed for the extrusion of sodium ions accumulated during glutamate uptake for rapid ECF glutamate clearance [117, 118, 135].”
Astroglial networking contributes to neurometabolic coupling
Escartin, C., & Rouach, N. (2013) · Frontiers in Neuroenergetics · doi:10.3389/fnene.2013.00004 · Cited by 66
“Glycolysis in astrocytes leads to rapid production of lactate, which is then transported to neurons, thereby fueling their energy needs (Pellerin and Magistretti, 1994).”
BackgroundMetabolic flexibility and cell hierarchy in metastatic cancer
Berridge, M. V., Herst, P. M., & Tan, A. S. (2010) · Mitochondrion · doi:10.1016/j.mito.2010.08.002 · Cited by 70
“Lactate is then taken up and converted to pyruvate by the activated neurons as a fuel for neuronal metabolism (Pellerin and Magistretti, 1994; Pellerin et al., 2007).”
BackgroundChan, O. T. M., Paranjape, S., Horblitt, A. M., Zhu, W., & Sherwin, R. S. (2013) · Diabetes · doi:10.2337/db13-0770 · Cited by 66
“Over a decade ago, Magistretti and colleagues (10,11) proposed the astrocyte-neuron lactate shuttle hypothesis, which posits that astrocytes provide adjacent neurons with lactate during periods of increased activation to help sustain increased metabolic demands.”
Insect models of central nervous system energy metabolism and its links to behavior
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“Moreover, similar to the honey bee, metabolic support by the glial cells is regulated via glutamate and ammonium released from the neurons (Lerchundi et al., 2015; Pellerin & Magistretti, 1994).”
BackgroundLactate Attenuates Synaptic Transmission and Affects Brain Rhythms Featuring High Energy Expenditure
Hollnagel, J., Cesetti, T., Schneider, J., Vazetdinova, A., Valiullina, F., Lewen, A., Rozov, A. V., & Kann, O. (2020) · iScience · doi:10.1016/j.isci.2020.101316 · Cited by 66
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“…glucose uptake from the abluminal side of the astrocytic endfeets as well as glucose and glycogen derived lactate production in astrocytes to meet the increased energy demand (Sickmann et al., 2009; Schousboe et al., 2010; Pellerin and Magistretti, 1994; Chatton et al., 2000; Porras et al., 2008).”
BackgroundMitochondria and the Brain: Bioenergetics and Beyond
Belenguer, P., Duarte, J. M. N., Schuck, P. F., & Ferreira, G. C. (2019) · Neurotoxicity Research · doi:10.1007/s12640-019-00061-7 · Cited by 69
Modulation of Glial Function in Health, Aging, and Neurodegenerative Disease
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Emerging role of glial cells in the control of body weight
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“Moreover, glutamate transport into astrocytes activates intracellular glycolysis, increasing lactate production and its distribution to neurons [105,109,133,134], thus controlling their nutrient availability.”
BackgroundBoussicault, L., Hérard, A., Calingasan, N. Y., Petit, F., Malgorn, C., Mérienne, N., Jan, C., Gaillard, M., Lerchundi, R., Barros, L. F., et al. (2014) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2014.110 · Cited by 65
Astrocyte metabolism following focal cerebral ischemia
Thorén, A. (2006) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600035 · Cited by 48
Roles and Regulation of Ketogenesis in Cultured Astroglia and Neurons Under Hypoxia and Hypoglycemia
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Emerging Roles for Glycogen in the CNS
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“The product of the glycolysis, lactate, is then transported out of the astrocyte and into the neurone where it is oxidatively metabolized (Pellerin and Magistretti, 1994).”
BackgroundResultTsai, S., Wu, H., Chen, P., Chen, Y., Yu, M., Wang, T.-F., Wu, S.-Y., Tzeng, S., & Kuo, Y. (2018) · Brain Research · doi:10.1016/j.brainres.2018.07.017 · Cited by 66
Nakamura, T., & Lipton, S. A. (2019) · Antioxidants and Redox Signaling · doi:10.1089/ars.2019.7916 · Cited by 67
“Concerning glucose metabolism in the brain, the Magistretti group proposed an interesting model termed the astrocyte–neuron lactate shuttle (72, 92), whereby astrocytes generate lactate via glycolysis and export lactate to neurons for conversion into pyruvate, feeding into the tricarboxylic acid (TCA) cycle, which app…”
BackgroundGlutamate uptake is decreased tardively in the spinal cord of FALS mice
Canton, T., Pratt, J., Stutzmann, J. M., Impérato, A., & Boireau, A. (1998) · Neuroreport · doi:10.1097/00001756-199803300-00001 · Cited by 65
Astrocytes and the delivery of glucose from plasma to neurons
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Glucose Metabolism in the Late Preterm Infant
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“The lactate shuttle, recently described as an alternate protective mechanism in the presence of hypoglycemia, consists of lactate being produced in astrocytes that then is transported as fuel to meet the energy requirements of neurons in the presence of limited glucose supply [40,41].”
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“The transfer of glucose-derived lactate from astrocytes to neurons is referred to as the astrocyte–neuron lactate shuttle (ANLS) hypothesis (Pellerin and Magistretti, 1994).”
BackgroundResultInfluentialSerres, S., Raffard, G., Franconi, J., & Merle, M. (2007) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600568 · Cited by 64
“This latter suggestion would be in agreement with the Glu uptake stimulation of astrocytic glycolysis (Pellerin and Magistretti, 1994), which leads to a higher production of lactate/ pyruvate in the astrocytic compartment (Serres et al, 2004).”
BackgroundResultRole of Na,K-ATPase α1 and α2 Isoforms in the Support of Astrocyte Glutamate Uptake
Illarionava, N. B., Brismar, H., Aperia, A. C., & Gunnarson, E. (2014) · PLoS ONE · doi:10.1371/journal.pone.0098469 · Cited by 64
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“It has been conjectured that increased synaptic activity stimulates glial metabolism and production of lactate that can be consumed by neurons [64,68] but simultaneously increased neuronal”
BackgroundThe role of astrocytes in the hypothalamic response and adaptation to metabolic signals
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“Supported by the astrocyte-neuron lactate shuttle hypothesis proposed by Pellerin and Magistretti (1994) (but see Magistretti, 2009; Barros and Deitmer, 2010), in which lactate release and concomitant glucose uptake in astrocytes is stimulated by sodium-coupled uptake of glutamate from glutamate…”
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“Further consideration in terms of the interpretation of the present study’s results also need to be given to the work of [33] that indicates that glutamate drives glycolysis in astrocytes, resulting in increased extracellular lactate, which can be used as a substrate for neurones in preference to glucose.”
BackgroundResultElizondo-Vega, R. J., Cortés‐Campos, C., Barahona, M. J., Pardo, C. C., Órdenes, P., Salgado, M., Oyarce, K., & García, M. D. L. Á. (2016) · Scientific Reports · doi:10.1038/srep33606 · Cited by 61
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“…by astrocytes which convert it into pyruvate which, after reduction to lactate, is released from astrocytes and serves neurons to produce energy in the process of oxidative phosphorylation (Pellerin & Magistretti, 1994; Pellerin & Magistretti, 2012; Serres, Bezancon, Franconi, & Merle, 2004).”
BackgroundThe micro-architecture of the cerebral cortex: Functional neuroimaging models and metabolism
Riera, J. J., Schousboe, A., Waagepetersen, H. S., Howarth, C., & Hyder, F. (2008) · NeuroImage · doi:10.1016/j.neuroimage.2007.12.051 · Cited by 63
“If indeed AGC1 is absent from astrocytes in the brain, one would expect that oxidative metabolism of Glc in this cellular compartment might be severely hampered (see below), in keeping with the astrocyte-neuron lactate shuttle (Pellerin and Magistretti, 1994).”
BackgroundDual-Gene, Dual-Cell Type Therapy against an Excitotoxic Insult by Bolstering Neuroenergetics
Bliss, T. M., Ip, M., Cheng, E., Minami, M., Pellerin, L., Magistretti, P. J., & Sapolsky, R. M. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.0805-04.2004 · Cited by 63
“This study and others have shown that glutamate enhances neuronal energetics in the presence of astrocytes, insofar as it increases glial lactate release (Pellerin and Magistretti, 1994) and neuronal lactate utilization (Schurr et al.”
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Elevated glutamate and lactate predict brain death after severe head trauma
Stefani, M. A., Modkovski, R., Hansel, G., Zimmer, E. R., Kopczynski, A., Muller, A. P., Strogulski, N. R., Rodolphi, M. S., Carteri, R. B., Schmidt, A. P., et al. (2017) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.416 · Cited by 62
“As previously stated, astrocytes take up glutamate in the synaptic space thereby triggering glycolysis and lactate production, which is shuttled to neurons.(15) The flux of these substrates in the body fluids has been explored in the clinical setting as biomarkers of neuroenergetic support, neuron-to-astrocyte interac…”
BackgroundNeuroprotective potential of astroglia
Liu, B., Teschemacher, A. G., & Kasparov, S. (2017) · Journal of Neuroscience Research · doi:10.1002/jnr.24140 · Cited by 65
Carter, S. F., Chiotis, K., Nordberg, A. K., & Rodriguez‐Vieitez, E. (2018) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-018-4217-7 · Cited by 63
Synaptic energy metabolism and neuronal excitability, in sickness and health
Oyarzábal, A., & Marin‐Valencia, I. (2019) · Journal of Inherited Metabolic Disease · doi:10.1002/jimd.12071 · Cited by 63
“This is the so-called astrocyte-neuronal lactate shuttle (ANLS).(80) While lactate has been shown to support neuronal metabolism at resting state,(81) the unidirectional flow of lactate from astrocytes to neurons and the contribution of lactate vs glucose to neuronal metabolism during stimulated activity remain contro…”
BackgroundIn vitro and ex vivo 13C-NMR Spectroscopy Studies of Pyruvate Recycling in Brain
Håberg, A., Qu, H., Bakken, I. J., Sande, L. M., Lr, W., Haraldseth, O., Unsgård, G., Aasly, J. O., & Sonnewald, U. (1998) · Developmental Neuroscience · doi:10.1159/000017335 · Cited by 62
Early 1H Magnetic Resonance Spectroscopy of Acute Head Injury: Four Cases
Condon, B. R., Oluoch-Olunya, D., Hadley, D. M., TEASDALE, G., & WAGSTAFF, A. (1998) · Journal of Neurotrauma · doi:10.1089/neu.1998.15.563 · Cited by 62
“It is also possible that lactate production is a normal response by astrocytes to the release of glutamate, not necessarily only a consequence of ischemia (Pellerin and Magistretti, 1994).”
Regulation of Lactate Production by FSH, IL1β, and TNFα in Rat Sertoli Cells
Riera, M. F., Meroni, S. B., Gómez, G. E., Schteingart, H. F., Pellizzari, E. H., & Cigorraga, S. B. (2001) · General and Comparative Endocrinology · doi:10.1006/gcen.2001.7619 · Cited by 62
Adenosine and cerebral ischemia: therapeutic future or death of a brave concept?
Lubitz, D. K. J. E. V. (1999) · European Journal of Pharmacology · doi:10.1016/s0014-2999(98)00788-2 · Cited by 62
Role of Fatty Acids β-Oxidation in the Metabolic Interactions Between Organs
Panov, A. V., Mayorov, V., & Dikalov, S. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252312740 · Cited by 63
Robinet, C., & Pellerin, L. (2009) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2009.208 · Cited by 62
“In addition, glutamatergic activity increases the production and release of lactate by astrocytes (Pellerin and Magistretti, 1994), and it has been purported that such an effect participates in a mechanism to provide lactate as an additional energy substrate to neurons to sustain their activity…”
Self-citationDynamic monitoring of cytosolic glucose in single astrocytes
Prebil, M., Vardjan, N., Jensen, J., Zorec, R., & Kreft, M. (2011) · Glia · doi:10.1002/glia.21161 · Cited by 61
Small is fast: astrocytic glucose and lactate metabolism at cellular resolution
Barros, L. F., Martín, A. S., Sotelo-Hitschfeld, T., Lerchundi, R., Fernández‐Moncada, I., Ruminot, I., Gutiérrez, R., Valdebenito, R., Ceballo, S., Alegría, K., et al. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00027 · Cited by 64
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
“Astrocytes are the only type of brain cell that store glycogen, and according to the evidence supporting the ‘lactate shuttle hypothesis’ produce and release lactate into the extracellular space to be taken up by neighbouring neurones (Pellerin & Magistretti, 1994).”
BackgroundInfluentialGoubert, E., Mircheva, Y., Lasorsa, F. M., Melon, C., Profilo, E., Sutera, J., Becq, H., Palmieri, F., Palmieri, L., Aniksztejn, L., et al. (2017) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2017.00149 · Cited by 61
“…is a highly consuming energy process as it is sensitive to Na+ and K+ electrochemical gradients, and the activation of the Na+/K+ATPase is essential to maintain these gradients (Pellerin and Magistretti, 1994; Magistretti and Pellerin, 1999; Chatton et al., 2000; Magistretti and Chatton, 2005).”
BackgroundDelgado, M. G., Oliva, C., López, E., Ibacache, A., Galaz, A., Delgado, R., Barros, L. F., & Sierralta, J. A. (2018) · Scientific Reports · doi:10.1038/s41598-018-19595-5 · Cited by 65
Modulation of hippocampal excitability via the hydroxycarboxylic acid receptor 1
Herrera‐López, G., & Galván, E. J. (2018) · Hippocampus · doi:10.1002/hipo.22958 · Cited by 63
“Therefore, lactate has a central function during compromised energetic states (Schurr et al., 1988; Takata et al., 2001) or during the metabolic coupling among astrocytes and neurons (Pellerin & Magistretti, 1994; Tsacopoulos & Magistretti, 1996).”
Cheng, H., Gang, X., Liu, Y., Wang, G., Zhao, X., & Wang, G. (2019) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00179.2019 · Cited by 63
Metabolic Coupling during Activation
Magistretti, P. J., & Pellerin, L. (1997) · Advances in experimental medicine and biology · doi:10.1007/978-1-4899-0056-2_18 · Cited by 61
Self-citationRooijackers, H. M. M., Wiegers, E. C., Tack, C. J., van der Graaf, M., & de Galan, B. E. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-015-2079-8 · Cited by 66
Neuron–astrocyte interactions in neurodegenerative diseases: Role of neuroinflammation
Rao, K. V. R., & Kielian, T. (2015) · Clinical and Experimental Neuroimmunology · doi:10.1111/cen3.12237 · Cited by 62
“Lactate is predominantly, if not exclusively, produced in astrocytes, and glutamate plays a central role in this process.(199) For example, during neurotransmission, neurons release glutamate into the synaptic cleft, which is rapidly cleared by astrocytes through selective glutamate transporters along with the release…”
BackgroundPeters, A. (2009) · Frontiers in Neuroenergetics · doi:10.3389/neuro.14.002.2009 · Cited by 62
“This explanation might be less surprising, if one takes into account that recent experimental evidence suggests the pull principle to constitute a natural process in neurometabolism (Pellerin and Magistretti, 1994).”
BackgroundShram, N. F., Netchiporouk, L. I., & Cespuglio, R. (2002) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2002.02081.x · Cited by 60
‘SNO’-Storms Compromise Protein Activity and Mitochondrial Metabolism in Neurodegenerative Disorders
Nakamura, T., & Lipton, S. A. (2017) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2017.10.004 · Cited by 60
“The group of Magistretti has proposed the “astrocyte-neuron lactate shuttle (ANLS)” model whereby lactate is released from astrocytes into the extracellular milieu and then shuttled into neurons [22, 24, 25] (Box 2).”
BackgroundLi, H., Liu, Y., Shang, L., Cai, J., Wu, J., Zhang, W., Pu, X., Dong, W., Qiao, T., & Li, K. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1820051116 · Cited by 62
“Despite the astrocyte-neuron lactate shuttle hypothesis (39) and the high expression of lactate dehydrogenase (this study), a burgeoning neuronal energy demand is hard to fulfill by the remarkably weakened OXPHOS due to Irp2 ablation.”
BackgroundCerebral metabolism and consciousness
Shulman, R. G., Hyder, F., & Rothman, D. L. (2003) · Comptes Rendus Biologies · doi:10.1016/s1631-0691(03)00071-4 · Cited by 61
Purinergic Signaling and Energy Homeostasis in Psychiatric Disorders
Lindberg, D. M., Shan, D., Ayers-Ringler, J. R., Oliveros, A., Benitez, J. C. A., Prieto, M. L., McCullumsmith, R. E., & Choi, D. (2015) · Current Molecular Medicine · doi:10.2174/1566524015666150330163724 · Cited by 65
A 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 62
“With Lactate being the end product, it is released into the interstitial space for neuronal uptake (Walz and Mukerji, 1988; Pellerin and Magistretti, 1994; Chuquet et al., 2010).”
BackgroundZhao, L., Dong, M., Ren, M., Li, C., Zheng, H. X., & Gao, H. (2018) · Molecular & Cellular Proteomics · doi:10.1074/mcp.ra118.000690 · Cited by 59
“Interestingly, previous studies have shown that lactate is involved in many physiological and pathological processes in the brain, such as appetite (54), mental disorders (55), neurotransmitter transporter function (56), and protection from brain damage (57), as well as cognition (38, 47, 51, 52).”
BackgroundZhao, X., Liu, L., Jiang, Y., Silva, M., Zhen, X., & Zheng, W. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/2524174 · Cited by 62
Characterization of Vimentin-Immunoreactive Astrocytes in the Human Brain
O’Leary, L. A., Davoli, M. A., Belliveau, C., Tanti, A., Ma, J. C., Farmer, W. T., Turecki, G., Murai, K. K., & Mechawar, N. (2020) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2020.00031 · Cited by 61
Salmina, A. B., Kharitonova, E. V., Gorina, Y. V., Тепляшина, Е. А., Malinovskaya, N. A., Хилажева, Е. Д., Mosiagina, A. I., Morgun, A. V., Shuvaev, А. N., Salmin, V. V., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094661 · Cited by 63
“ANLS was initially observed in glutamate-stimulated neurons [50], but some later studies revealed that activated neurons might not be so much dependent on lactate supply from astroglia since they prefer to utilize glucose to support their energetic needs [51].”
BackgroundA lactate-dependent shift of glycolysis mediates synaptic and cognitive processes in male mice
Fernández‐Moncada, I., Lavanco, G., Fundazuri, U. B., Bollmohr, N., Mountadem, S., Tor, T. D., Hachaguer, P., Julio‐Kalajzić, F., Gisquet, D., Serrat, R., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-51008-2 · Cited by 63
Self-citationBrain energy homeostasis: the evolution of the astrocyte-neuron lactate shuttle hypothesis
Kim, Y., Dube, S. E., & Park, C. B. (2024) · Korean Journal of Physiology and Pharmacology · doi:10.4196/kjpp.24.388 · Cited by 65
Age‐related changes in neuronal glucose uptake in response to glutamate and β‐amyloid
Patel, J. R., & Brewer, G. J. (2003) · Journal of Neuroscience Research · doi:10.1002/jnr.10602 · Cited by 59
“There is evidence linking deficits in brain glucose utilization with aging (Willis et al., 2002) and neurodegenerative disease such as Alzheimer’s disease (AD) and Parkinson’s (Pettegrew et al., 1994; Mattson et al., 1999; De Santi et al., 2001; Uemura and Greenlee, 2001).”
BackgroundDash, M. B., Tononi, G., & Cirelli, C. (2012) · SLEEP · doi:10.5665/sleep.1950 · Cited by 59
Christensen, B., Arbour, L. T., Tran, P. V., Leclerc, D., Sabbaghian, N., Platt, R. W., Gilfix, B. M., Rosenblatt, D. S., Gravel, R. A., Forbes, P. A., et al. (1999) · American Journal of Medical Genetics · doi:10.1002/(sici)1096-8628(19990521)84:2 · Cited by 305
Ca2+ as the prime trigger of aerobic glycolysis in astrocytes
Horvat, A., Muhič, M., Smolič, T., Begić, E., Zorec, R., Kreft, M., & Vardjan, N. (2021) · Cell Calcium · doi:10.1016/j.ceca.2021.102368 · Cited by 60
Altered substrate metabolism in neurodegenerative disease: new insights from metabolic imaging
Cleland, N. R. W., Al‐Juboori, S. I., Dobrinskikh, E., & Bruce, K. D. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02305-w · Cited by 62
Rothman, D. L., Dienel, G. A., Behar, K. L., Hyder, F., DiNuzzo, M., Giove, F., & Mangia, S. (2022) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x211064399 · Cited by 58
“As stated above, under conditions of complete glucose sparing, glycogenolysis replaces incremental astrocytic glucose metabolism (i.e., DCMRglc-A ¼ 0), thus the maximum rate and incremental rate of neuronal glucose consumption are respectively given by: CMRglc-N-max ¼ CMRglc-N-RA þ DCMRglc-N-max ¼ VGT-max CMRglc-A-RA…”
BackgroundAstrocytes, reactive astrogliosis, and glial scar formation in traumatic brain injury
Cieri, M. B., & Ramos, A. J. (2024) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-23-02091 · Cited by 66
“Astrocytes play a key role in supporting neuronal metabolism, this has been proposed by the astrocyte-to-neuron lactate shuttle model to sustain neuronal mitochondrial function necessary for high neuronal energy demands (Pellerin and Magistretti, 1994; Magistretti and Allaman, 2018).”
BackgroundVolianitis, S., Fabricius-Bjerre, A., Overgaard, A., Strømstad, M., Bjarrum, M., Carlson, C., Petersen, N., Rasmussen, P. V., Secher, N. H., & Nielsen, H. B. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2007.142273 · Cited by 58
“In addition to lactate taken up from the circulation, neurones can be fuelled by lactate produced in the astrocytes, which are mainly glycolytic at the expense of astrocytic glycogen or arterial glucose (Pellerin & Magistretti, 1994).”
BackgroundLugo‐Morales, L. Z., Loziuk, P. L., Corder, A. K., Toups, J. V., Roberts, J. G., McCaffrey, K. A., & Sombers, L. A. (2013) · Analytical Chemistry · doi:10.1021/ac4017852 · Cited by 58
Metabolic Flux and Compartmentation Analysis in the Brain In vivo
Lanz, B., Rolf Gruetter, A., & Duarte, J. M. N. (2013) · Frontiers in Endocrinology · doi:10.3389/fendo.2013.00156 · Cited by 58
Basic Science Review: Nitric Oxide—Releasing Prosthetic Materials
Varu, V. N., Tsihlis, N. D., & Kibbe, M. R. (2008) · Vascular and Endovascular Surgery · doi:10.1177/1538574408322752 · Cited by 59
Riera, M. F., Meroni, S. B., Schteingart, H. F., Pellizzari, E. H., & Cigorraga, S. B. (2002) · Journal of Endocrinology · doi:10.1677/joe.0.1730335 · Cited by 58
“Interestingly, a similar metabolic co-operation between astrocytes and neurons has been demonstrated (Pellerin & Magistretti 1994).”
Background
Metadata
- Authors
- Pellerin, L., & Magistretti, P. J.
- Affiliations
- University of Lausanne (CH)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1994-10-25
- Volume
- 91
- Issue
- 22
- Pages
- 10625-10629
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC45074
- OpenAlex
- W2092635505
- Cited by
- 2,927
- References
- 41
- Citations by year
- 2026: 143 · 2025: 146 · 2024: 138 · 2023: 137 · 2022: 147 · 2021: 168 · 2020: 122 · 2019: 133 · 2018: 109 · 2017: 113 · 2016: 107 · 2015: 116 · 2014: 126 · 2013: 91 · 2012: 88
- FWCI
- 10.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (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
- glutamate uptake, astrocytes, aerobic glycolysis, Na+/K+-ATPase, neuronal activity, glucose utilization, lactic acid production, nonoxidative glucose metabolism, astrocyte-neuron interaction
- MeSH terms
- Sodium-Potassium-Exchanging ATPase, Aerobiosis, Animals, Animals, Newborn, Astrocytes, Biological Transport, Brain, Cells, Cultured, Cerebral Cortex, Deoxyglucose, Glycolysis, Lactates, Models, Neurological, Neurons, Radionuclide Imaging, Tritium, Excitatory Amino Acid Antagonists, Glutamic Acid, Mice
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