CoChat
Sign Up
Cited by 134Neuroscience and Neuropharmacology ResearchAmino Acid Enzymes and MetabolismCancer, Hypoxia, and Metabolism

Unraveling the complex metabolic nature of astrocytes

Open access
Bouzier-Sore, Anne-Karine, Pellerin, Luc·2013·Frontiers in Cellular Neuroscience
DOI 10.3389/fncel.2013.00179PMC PMC3795301
Open this paper in CoChat — free accountOpen PDF

Abstract

Since the initial description of astrocytes by neuroanatomists of the nineteenth century, a critical metabolic role for these cells has been suggested in the central nervous system. Nonetheless, it took several technological and conceptual advances over many years before we could start to understand how they fulfill such a role. One of the important and early recognized metabolic function of astrocytes concerns the reuptake and recycling of the neurotransmitter glutamate. But the description of this initial property will be followed by several others including an implication in the supply of energetic substrates to neurons. Indeed, despite the fact that like most eukaryotic non-proliferative cells, astrocytes rely on oxidative metabolism for energy production, they exhibit a prominent aerobic glycolysis capacity. Moreover, this unusual metabolic feature was found to be modulated by glutamatergic activity constituting the initial step of the neurometabolic coupling mechanism. Several approaches, including biochemical measurements in cultured cells, genetic screening, dynamic cell imaging, nuclear magnetic resonance spectroscopy and mathematical modeling, have provided further insights into the intrinsic characteristics giving rise to these key features of astrocytes. This review will provide an account of the different results obtained over several decades that contributed to unravel the complex metabolic nature of astrocytes that make this cell type unique.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3389/fncel.2013.00179

Cites

6 of 6 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 119

  1. Allaman I. Gavillet M. Bélanger M. Laroche T. Viertl D. Lashuel H. A. (2010). Amyloid-beta aggregates cause alterations of astrocytic metabolic phenotype: impact on neuronal viability. J. Neurosci. 30 3326– 3338 10.1523/JNEUROSCI.5098-09.2010 20203192 PMC6634099 · DOI
  2. Alves P. M. McKenna M. C. Sonnewald U. (1995). Lactate metabolism in mouse brain astrocytes studied by [13C]NMR spectroscopy. Neuroreport 6 2201– 2204 10.1097/00001756-199511000-00024 8595202 · DOI
  3. Amaral A. I. Teixeira A. P. Hakonsen B. I. Sonnewald U. Alves P. M. (2011). A comprehensive metabolic profile of cultured astrocytes using isotopic transient metabolic flux analysis and C-labeled glucose. Front. Neuroenergetics 3: 5 10.3389/fnene.2011.00005 PMC3171112 21941478 · DOI
  4. Andriezen W. L. (1893a). The neuroglia elements of the brain. Br. Med. J. 2 227– 230 10.1136/bmj.2.1700.227 PMC2422013 20754383 · DOI
  5. Attwell D. Laughlin S. B. (2001). An energy budget for signaling in the grey matter of the brain. J. Cereb. Blood Flow Metab. 21 1133– 1145 10.1097/00004647-200110000-00001 11598490 · DOI · Paper page
  6. Aubert A. Costalat R. (2005). Interaction between astrocytes and neurons studied using a mathematical model of compartmentalized energy metabolism. J. Cereb. Blood Flow Metab. 25 1476– 1490 10.1038/sj.jcbfm.9600144 15931164 · DOI
  7. Aubert A. Costalat R. Magistretti P. J. Pellerin L. (2005). Brain lactate kinetics: modeling evidence for neuronal lactate uptake upon activation. Proc. Natl. Acad. Sci. U.S.A. 102 16448– 16453 10.1073/pnas.0505427102 16260743 PMC1297516 · DOI
  8. Azarias G. Perreten H. Lengacher S. Poburko D. Demaurex N. Magistretti P. J. (2011). Glutamate transport decreases mitochondrial pH and modulates oxidative metabolism in astrocytes. J. Neurosci. 31 3550– 3559 10.1523/JNEUROSCI.4378-10.2011 21389211 PMC6622778 · DOI · Paper page
  9. Badar-Goffer R. S. Ben-Yoseph O. Bachelard H. S. Morris P. G. (1992). Neuronal-glial metabolism under depolarizing conditions. A 13C-n.m.r. study. Biochem. J. 282(Pt 1) 225– 230 1540138 PMC1130911
  10. Bak L. K. Sickmann H. M. Schousboe A. Waagepetersen H. S. (2005). Activity of the lactate-alanine shuttle is independent of glutamate-glutamine cycle activity in cerebellar neuronal-astrocytic cultures. J. Neurosci. Res. 79 88– 96 10.1002/jnr.20319 15578733 · DOI
  11. Bak L. K. Walls A. B. Schousboe A. Ring A. Sonnewald U. Waagepetersen H. S. (2009). Neuronal glucose but not lactate utilization is positively correlated with NMDA-induced neurotransmission and fluctuations in cytosolic Ca2+ levels. J. Neurochem. 109(Suppl. 1) 87– 93 10.1111/j.1471-4159.2009.05943.x 19393013 · DOI · Paper page
  12. Barros L. F. Courjaret R. Jakoby P. Loaiza A. Lohr C. Deitmer J. W. (2009). Preferential transport and metabolism of glucose in Bergmann glia over Purkinje cells: a multiphoton study of cerebellar slices. Glia 57 962– 970 10.1002/glia.20820 19062182 · DOI
  13. Benington J. H. Heller H. C. (1995). Restoration of brain energy metabolism as the function of sleep. Prog. Neurobiol. 45 347– 360 10.1016/0301-0082(94)00057-O 7624482 · DOI
  14. Bergersen L. Rafiki A. Ottersen O. P. (2002). Immunogold cytochemistry identifies specialized membrane domains for monocarboxylate transport in the central nervous system. Neurochem. Res. 27 89– 96 10.1023/A:1014806723147 11926280 · DOI
  15. Berkich D. A. Ola M. S. Cole J. Sweatt A. J. Hutson S. M. LaNoue K. F. (2007). Mitochondrial transport proteins of the brain. J. Neurosci. Res. 85 3367– 3377 10.1002/jnr.21500 17847082 · DOI
  16. Berl S. Takagaki G. Clarke D. D. Waelsch H. (1962). Metabolic compartments in vivo. Ammonia and glutamic acid metabolism in brain and liver. J. Biol. Chem. 237 2562– 2569 13867916
  17. Bittar P. G. Charnay Y. Pellerin L. Bouras C. Magistretti P. J. (1996). Selective distribution of lactate dehydrogenase isoenzymes in neurons and astrocytes of human brain. J. Cereb. Blood Flow Metab. 16 1079– 1089 10.1097/00004647-199611000-00001 8898679 · DOI · Paper page
  18. Bittner C. X. Loaiza A. Ruminot I. Larenas V. Sotelo-Hitschfeld T. Gutierrez R. (2010). High resolution measurement of the glycolytic rate. Front. Neuroenergetics 2: 26 10.3389/fnene.2010.00026 PMC2947927 20890447 · DOI
  19. Bittner C. X. Valdebenito R. Ruminot I. Loaiza A. Larenas V. Sotelo-Hitschfeld T. (2011). Fast and reversible stimulation of astrocytic glycolysis by K+ and a delayed and persistent effect of glutamate. J. Neurosci. 31 4709– 4713 10.1523/JNEUROSCI.5311-10.2011 21430169 PMC6622916 · DOI
  20. Bliss T. M. Ip M. Cheng E. Minami M. Pellerin L. Magistretti P. J. (2004). Dual-gene, dual-cell type therapy against excitotoxic insult by bolstering neuroenergetics. J. Neurosci. 24 8202– 8208 10.1523/JNEUROSCI.0805-04.2004 PMC6729663 15240812 · DOI
  21. Bonvento G. Sibson N. Pellerin L. (2002). Does glutamate image your thoughts ? Trends Neurosci. 25 359– 364 10.1016/S0166-2236(02)02168-9 12079764 · DOI
  22. Boumezbeur F. Petersen K. F. Cline G. W. Mason G. F. Behar K. L. Shulman G. I. (2010). The contribution of blood lactate to brain energy metabolism in humans measured by dynamic 13C nuclear magnetic resonance spectroscopy. J. Neurosci. 30 13983– 13991 10.1523/JNEUROSCI.2040-10.2010 20962220 PMC2996729 · DOI
  23. Bouzier A. K. Thiaudiere E. Biran M. Rouland R. Canioni P. Merle M. (2000). The metabolism of [3-(13)C]lactate in the rat brain is specific of a pyruvate carboxylase-deprived compartment. J. Neurochem. 75 480– 486 10.1046/j.1471-4159.2000.0750480.x 10899922 · DOI
  24. Bouzier-Sore A. K. Voisin P. Bouchaud V. Bezancon E. Franconi J. M. Pellerin L. (2006). Competition between glucose and lactate as oxidative energy substrates in both neurons and astrocytes: a comparative NMR study. Eur. J. Neurosci. 24 1687– 1694 10.1111/j.1460-9568.2006.05056.x 17004932 · DOI · Paper page
  25. Bouzier-Sore A. K. Voisin P. Canioni P. Magistretti P. J. Pellerin L. (2003). Lactate is a preferential oxidative energy substrate over glucose for neurons in culture. J. Cereb. Blood Flow Metab. 23 1298– 1306 10.1097/01.WCB.0000091761.61714.25 14600437 · DOI · Paper page
  26. Brö er S. Brookes N. (2001). Transfer of glutamine between astrocytes and neurons. J. Neurochem. 77 705– 719 10.1046/j.1471-4159.2001.00322.x 11331400 · DOI
  27. Brookes N. Yarowsky P. J. (1985). Determinants of deoxyglucose uptake in cultured astrocytes: the role of the sodium pump. J. Neurochem. 44 473– 479 10.1111/j.1471-4159.1985.tb05438.x 2578179 · DOI
  28. Brix B. Mesters J. R. Pellerin L. Jöhren O. (2012). Endothelial cell-derived ntric oxide enhances aerobic glycolysis in astrocytes via HIF-1a-mediated target gene activation. J. Neurosci. 32 9727– 9735 10.1523/JNEUROSCI.0879-12.2012 22787058 PMC6622272 · DOI
  29. Danbolt N. C. (2001). Glutamate uptake. Prog. Neurobiol. 65 1– 105 10.1016/S0301-0082(00)00067-8 11369436 · DOI · Paper page
  30. DiNuzzo M. Mangia S. Maraviglia B. Giove F. (2010a). Changes in glucose uptake rather than lactate shuttle take center stage in subserving neuroenergetics: evidence from mathematical modeling. J. Cereb. Blood Flow Metab. 30 586– 602 10.1038/jcbfm.2009.232 19888285 PMC2949148 · DOI
  31. DiNuzzo M. Mangia S. Maraviglia B. Giove F. (2010b). Glycogenolysis in astrocytes supports blood-borne glucose channeling not glycogen-derived lactate shuttling to neurons: evidence from mathematical modeling. J. Cereb. Blood Flow Metab. 30 1895– 1904 10.1038/jcbfm.2010.151 20827264 PMC3002884 · DOI
  32. Dringen R. Hamprecht B. (1993). Glycogen in astrocytes: possible function as lactate supply for neighboring cells. Brain Res. 623 208– 214 10.1016/0006-8993(93)91429-V 8221102 · DOI
  33. Erlichman J. S. Hewitt A. Damon T. L. Hart M. Kurascz J. Li A. (2008). Inhibition of monocarboxylate transporter 2 in the retrotrapezoid nucleus in rats – a test of the astrocyte-neuron lactate-shuttle hypothesis. J. Neurosci. 28 4888– 4896 10.1523/JNEUROSCI.5430-07.2008 18463242 PMC2645067 · DOI
  34. Escartin C. Pierre K. Colin A. Brouillet E. Delzescaux T. Guillemier M. (2007). Activation of astrocytes by CNTF induces metabolic plasticity and increases resistance to metabolic insults. J. Neurosci. 27 7094– 7104 10.1523/JNEUROSCI.0174-07.2007 17611262 PMC6794576 · DOI
  35. Fitzpatrick S. M. Hetherington H. P. Behar K. L. Shulman R. G. (1990). The flux from glucose to glutamate in the rat brain in vivo as determined by 1H-observed, 13C-edited NMR spectroscopy. J. Cereb. Blood Flow Metab. 10 170– 179 10.1038/jcbfm.1990.32 1968068 · DOI
  36. Galeffi F. Foster K. A. Sadgrove M. P. Beaver C. J. Turner D. A. (2007). Lactate uptake contributes to the NAD(P)H biphasic response and tisue oxygen response during synaptic stimulation in area CA1 of rat hippocampal slices. J. Neurochem. 103 2449– 2461 10.1111/j.1471-4159.2007.04939.x 17931363 PMC3340603 · DOI
  37. Genc S. Kurnaz I. A. Ozligen M. (2011). Astrocyte-neuron lactate shuttle may boost more ATP supply to the neuron under hypoxic conditions – in silico study supported by in vitro expression data. BMC Syst. Biol. 3: 162 10.1186/1752-0509-5-162 PMC3202240 21995951 · DOI
  38. Giaume C. Koulakoff A. Roux L. Holcman D. Rouach N. (2010). Astroglial networks: a step further in neuroglial and gliovascular interactions. Nat. Neurosci. Rev. 11 87– 99 10.1038/nrn2757 20087359 · DOI
  39. Gordon G. R. Choi H. B. Rungta R. L. Elis-Davies G. C. MacVicar B. A. (2008). Brain metabolism dictates the polarity of astrocyte control over arterioles. Nature 456 745– 749 10.1038/nature07525 18971930 PMC4097022 · DOI
  40. Halim N. D. Mcfate T. Mohyeldin A. Okagaki P. Korotchkina L. G. Patel M. S. (2010). Phosphorylation status of pyruvate dehydrogenase distinguishes metabolic phenotypes of cultured rat brain astrocytes and neurons. Glia 58 1168– 1176 20544852 PMC2915787
  41. Hamberger A. Hyden H. (1963). Inverse enzymatic changes in neurons and glia during increased function and hypoxia. J. Cell Biol. 16 521– 525 10.1083/jcb.16.3.521 13952284 PMC2106232 · DOI
  42. Hassel B. Brathe A. (2000). Cerebral metabolism of lactate in vivo: evidence for neuronal pyruvate carboxylation. J. Cereb. Blood Flow Metab. 20 327– 336 10.1097/00004647-200002000-00014 10698070 · DOI
  43. Herrero-Mendez A. Almeida A. Fernandez E. Maestre C. Moncada S. Bolanos J. P. (2009). The bioenergetic and antioxidant status of neurons is controlled by continuous degradation of a key glycolytic enzyme by APC/C-Cdh1. Nat. Cell Biol. 11 747– 752 10.1038/ncb1881 19448625 · DOI · Paper page
  44. Hof P. R. Pascale E. Magistretti P. J. (1988). K+ at concentrations reached in the extracellular space during neuronal activity promotes a Ca2+-dependent glycogen hydrolysis in mouse cerebral cortex. J. Neurosci. 8 1922– 1928 3385482 PMC6569342
  45. Hyden H. (1959). Quantitative assay of compounds in isolated, fresh nerve cells and glial cells from control and stimulated animals. Nature 184 433– 435 10.1038/184433a0 14405713 · DOI
  46. Hyden H. Rapallino M. V. Cupello A. (2000). Unraveling of important neurobiological mechanisms by the use of pure, fully differentiated neurons obtained from adult animals. Prog. Neurobiol. 60 471– 499 10.1016/S0301-0082(99)00035-0 10697074 · DOI
  47. Itoh Y. Esaki T. Shimoji K. Cook M. Law M. J. Kaufman E. (2003). Dichloroacetate effects on glucose and lactate oxidation by neurons and astroglia in vitro and on glucose utilization by brain in vivo. Proc. Natl. Acad. Sci. U.S.A. 100 4879– 4884 10.1073/pnas.0831078100 12668764 PMC153649 · DOI · Paper page
  48. Jakoby P. Schmidt E. Ruminot I. Gutierrez R. Barros L. F. Deitmer J. W. (2013). Higher transport and metabolism of glucose in astrocytes compared with neurons: a multiphoton study of hippocampal and cerebellar tissue slices. Cereb. Cortex [Epub ahead of print] 23042735
  49. Jolivet R. Allaman I. Pellerin L. Magistretti P. J. Weber B. (2010). Comment on recent modeling studies of astrocyte-neuron metabolic interactions. J. Cereb. Blood Flow Metab. 30 1982– 1986 10.1038/jcbfm.2010.132 20700131 PMC3002878 · DOI
  50. Jolivet R. Magistretti P. J. Weber B. (2009). Deciphering neuron-glia compartmentalization in cortical energy metabolism. Front. Neuroenergetics 1: 4 10.3389/neuro.14.004.2009 PMC2715922 19636395 · DOI
  51. Kacem K. Lacombe P. Seylaz J. Bonvento G. (1998). Structural organization of the perivascular astrocyte endfeet and their relationship with the endothelial glucose transporter: a confocal microscopy study. Glia 23 1– 10 10.1002/(SICI)1098-1136(199805)23:1<1::AID-GLIA1>3.0.CO;2-B 9562180 · DOI
  52. Kasischke K. A. Vishwasrao H. Fischer P. J. Zipfel W. R. Webb W. W. (2004). Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis. Science 305 99– 103 10.1126/science.1096485 15232110 · DOI · Paper page
  53. Kettenmann H. Verkhratsky A. (2008). Neuroglia: the 150 years after. Trends Neurosci. 31 653– 659 10.1016/j.tins.2008.09.003 18945498 · DOI
  54. Kunnecke B. Cerdan S. Seelig J. (1993). Cerebral metabolism of [1,2-13C2]glucose and [U-13C4]3-hydroxybutyrate in rat brain as detected by 13C NMR spectroscopy. NMR Biomed. 6 264– 277 10.1002/nbm.1940060406 8105858 · DOI
  55. Lam T. K. Gutierrez-Juarez R. Pocai A. Rossetti L. (2005). Regulation of blood glucose by hypothalamic pyruvate metabolism. Science 309 943– 947 10.1126/science.1112085 16081739 · DOI · Paper page
  56. Laughton J. D. Bittar P. Charnay Y. Pellerin L. Kovari E. Magistretti P. J. (2007). Metabolic compartmentation in the human cortex and hippocmpus: evidence for a cell- and region-specific localization of lactate dehydrogenase 5 and pyruvate dehydrogenase. BMC Neurosci. 8: 35 10.1186/1471-2202-8-35 PMC1899510 17521432 · DOI
  57. Lebon V. Petersen K. F. Cline G. W. Shen J. Mason G. F. Dufour S. (2002). Astroglial contribution to brain energy metabolism in humans revealed by 13C nuclear magnetic resonance spectroscopy: elucidation of the dominant pathway for neurotransmitter glutamate repletion and measurement of astrocytic oxidative metabolism. J. Neurosci. 22 1523– 1531 11880482 PMC2995528
  58. Leo G. C. Driscoll B. F. Shank R. P. Kaufman E. (1993). Analysis of [1-13C]D-glucose metabolism in cultured astrocytes and neurons using nuclear magnetic resonance spectroscopy. Dev. Neurosci. 15 282– 288 10.1159/000111346 7805580 · DOI
  59. Lovatt D. Sonnewald U. Waagepetersen H. S. Schousboe A. He W. Lin J. H. (2007). The transcriptome and metabolic gene signature of protoplasmic astrocytes in the adult murine cortex. J. Neurosci. 27 12255– 12266 10.1523/JNEUROSCI.3404-07.2007 17989291 PMC6673251 · DOI
  60. Magistretti P. J. Morrison P. J. Shoemaker W. J. Sapin V. Bloom F. E. (1981). Vasoactive intestinal polypeptide induces glycogenolysis in mouse cortical slices: a possible regulatory mechanism for the local control of energy metabolism. Proc. Natl. Acad. Sci. U.S.A. 78 6535– 6539 10.1073/pnas.78.10.6535 6118864 PMC349075 · DOI
  61. Mangia S. DiNuzzo M. Giove F. Carruthers A. Simpson I. A. Vannucci S. J. (2011). Response to `comment on recent modeling studies of astrocyte-neuron metabolic interactions': much ado about nothing. J. Cereb. Blood Flow Metab. 31 1346– 1353 10.1038/jcbfm.2011.29 21427731 PMC3130323 · DOI · Paper page
  62. Mangia S. Simpson I. A. Vannucci S. J. Carruthers A. (2009). The in vivo neuron-to-astrocyte lactate shuttle in human brain: evidence from modeling of measured lactate levels during visual stimulation. J. Neurochem. 109(Suppl. 1) 55– 62 10.1111/j.1471-4159.2009.06003.x PMC2679179 19393009 · DOI
  63. Martin M. Portais J. C. Labouesse J. Canioni P. Merle M. (1993). [1-13C]glucose metabolism in rat cerebellar granule cells and astrocytes in primary culture. Evaluation of flux parameters by 13C- and 1H-NMR spectroscopy. Eur. J. Biochem. 217 617– 625 10.1111/j.1432-1033.1993.tb18284.x 7901011 · DOI
  64. Martinez-Hernandez A. Bell K. P. Norenberg M. D. (1977). Glutamine synthetase: glial localization in brain. Science 195 1356– 1358 10.1126/science.14400 14400 · DOI
  65. Mason G. F. Gruetter R. Rothman D. L. Behar K. L. Shulman R. G. Novotny E. J. (1995). Simultaneous determination of the rates of the TCA cycle, glucose utilization, alpha-ketoglutarate/glutamate exchange, and glutamine synthesis in human brain by NMR. J. Cereb. Blood Flow Metab. 15 12– 25 10.1038/jcbfm.1995.2 7798329 · DOI
  66. Mason G. F. Rothman D. L. Behar K. L. Shulman R. G. (1992). NMR determination of the TCA cycle rate and alpha- ketoglutarate/glutamate exchange rate in rat brain. J. Cereb. Blood Flow Metab. 12 434– 447 10.1038/jcbfm.1992.61 1349022 · DOI
  67. Mayevsky A. Rogatsky G. G. (2007). Mitochondrial function in vivo evaluated by NADH fluorescence: from animal models to human studies. Am. J. Physiol. 292 C615– C640 10.1152/ajpcell.00249.2006 16943239 · DOI
  68. McCarthy K. D de Vellis J. (1980). Preparation of separate astroglial and oligodendroglial cell cultures from rat cerebral tissue. J. Cell Biol. 85 890– 902 10.1083/jcb.85.3.890 6248568 PMC2111442 · DOI
  69. McKenna M. C. Sonnewald U. Huang X. Stevenson J. Zielke H. R. (1996). Exogenous glutamate concentration regulates the metabolic fate of glutamate in astrocytes. J. Neurochem. 66 386– 393 10.1046/j.1471-4159.1996.66010386.x 8522979 · DOI
  70. Neves A. Costalat R. Pellerin L. (2012). Determinants of brain cell metabolic phenotypes and energy substrate utilization unraveled with a modeling approach. PLoS Comput. Biol. 8: e1002686 10.1371/journal.pcbi.1002686 PMC3441424 23028284 · DOI
  71. Newman L. A. Korol D. L. Gold P. E. (2011). Lactate produced by glycogenolysis in astrocytes regulates memory processing. PLoS ONE 6: e28427 10.1371/journal.pone.0028427 PMC3236748 22180782 · DOI
  72. O’Brien J. Kla K. M. Hopkins I. B. Malecki E. A. McKenna M. C. (2007). Kinetic parameters and lactate dehydrogenase isozyme activities support possible lactate utilization by neurons. Neurochem. Res. 32 597– 607 10.1007/s11064-006-9132-9 17006762 · DOI
  73. Occhipinti R. Puchowicz M. A. LaManna J. C. Somersalo E. Calvetti D. (2007). Statistical analysis of metabolic pathways of brain metabolism at steady state. Ann. Biomed. Eng. 35 886– 902 10.1007/s10439-007-9270-5 17385046 · DOI
  74. O’Dowd B. S. Gibbs M. E. Ng K. T. Hertz E. Hertz L. (1994a). Astrocytic glycogenolysis energizes memory processes in neonate chicks. Dev. Brain Res. 78 137– 141 10.1016/0165-3806(94)90018-3 8004768 · DOI
  75. O’Dowd B. S. Gibbs M. E. Sedman G. L. Ng K. T. (1994b). Astrocytes implicated in the energizing of intermediate memory processes in neonate chicks. Cogn. Brain Res. 2 93– 102 10.1016/0926-6410(94)90006-X 7833696 · DOI
  76. Pardo B. Rodrigues T. B. Contreras L. Garzon M. Llorente-Folch I. Kobayashi K. (2011). Brain glutamine synthesis requires neuronal-born aspartate as amino donor for glial glutamate formation. J. Cereb. Blood Flow Metab. 31 90– 101 10.1038/jcbfm.2010.146 20736955 PMC3049464 · DOI
  77. Parsons M. P. Hirasawa M. (2010). ATP-sensitive potassium channel-mediated effect on orexin neurons: implications for brain energetics during arousal. J. Neurosci. 30 8061– 8070 10.1523/JNEUROSCI.5741-09.2010 20554857 PMC6634592 · DOI
  78. Patel A. J. Hunt A. Gordon R. D. Balazs R. (1982). The activities in different neural cell types of certain enzymes associated with the metabolic compartmentation glutamate. Brain Res. 256 3– 11 6124308
  79. Pellerin L. Bergersen L. H. Halestrap A. P. Pierre K. (2005). Cellular and subcellular distribution of monocarboxylate transporters in cultured brain cells and in the adult brain. J. Neurosci. Res. 79 55– 64 10.1002/jnr.20307 15573400 · DOI
  80. Pellerin L. Magistretti P. J. (2003). How to balance the brain energy budget while spending glucose differently. J. Physiol. 546 325 10.1113/jphysiol.2002.035105 PMC2342533 12527720 · DOI
  81. Pellerin L. Magistretti P. J. (2012). Sweet sixteen for ANLS. J. Cereb. Blood Flow Metab. 32 152– 166 10.1038/jcbfm.2011.149 PMC3390819 22027938 · DOI
  82. Porras O. H. Loaiza A. Barros L. F. (2004). Glutamate mediates acute glucose transport inhibition in hippocampal neurons. J. Neurosci. 24 9669– 9673 10.1523/JNEUROSCI.1882-04.2004 15509754 PMC6730152 · DOI · Paper page
  83. Preece N. E. Cerdan S. (1996). Metabolic precursors and compartmentation of cerebral GABA in vigabatrin-treated rats. J. Neurochem. 67 1718– 1725 10.1046/j.1471-4159.1996.67041718.x 8858958 · DOI
  84. Ramos M. del Arco A. Pardo B. Martinez-Serrano A. Martinez- Morales J. R. Kobayashi K. (2003). Developmental changes in the Ca2+-regulated mitochondrial aspartate-glutamate carrier aralar1 in brain and prominent expression in the spinal cord. Dev. Brain Res. 143 33– 46 10.1016/S0165-3806(03)00097-X 12763579 · DOI
  85. Reinert K. C. Gao W. Chen G. Wang X. Peng Y. P. Ebner T. J. (2011). Cellular and metabolic origins of flavoprotein autofluorescence in the cerebellar cortex in vivo. Cerebellum 10 585– 599 10.1007/s12311-011-0278-x 21503591 PMC4126810 · DOI
  86. Requardt R. P. Wilhelm F. Rillich J. Winkler U. Hirrlinger J. (2010). The biphasic NAD(P)H fluorescence response of astrocytes to dopamine reflects the metabolic actions of oxidative phosphorylation and glycolysis. J. Neurochem. 115 483– 492 10.1111/j.1471-4159.2010.06940.x 20698931 · DOI
  87. Rodrigues T. B. Sierra A. Ballesteros P. Cerdan S. (2012). “Pyruvate transport and metabolism in the central nervous system,” in Neural Metabolism In Vivo eds Choi I.-Y. Gruetter R. (Berlin: Springer) 715– 753
  88. Rodriguez-Rodriguez P. Almeida A. Bolanos J. P. (2013). Brain energy metabolism in glutamate-receptor activation and excitotoxicity: role for APC/C-Cdh1 in the balance glycolysis/pentose phosphate pathway. Neurochem. Int. 62 750– 756 10.1016/j.neuint.2013.02.005 23416042 · DOI
  89. Rodriguez-Rodriguez P. Fernandez E. Almeida A. Bolanos J. P. (2012). Excitotoxic stimulus stabilizes PFKFB3 causing pentose-phosphate pathway to glycolysis switch and neurodegeneration. Cell Death Differ. 19 1582– 1589 10.1038/cdd.2012.33 22421967 PMC3438489 · DOI
  90. Ruminot I. Gutiérrez R. Pena-Münzenmayer G. Anazco C. Sotelo-Hitschfeld T. Lerchundi R. (2011). NBCe1 mediates the acute stimulation of astrocytic glycolysis by extracellular K+. J. Neurosci. 31 14264– 14271 10.1523/JNEUROSCI.2310-11.2011 21976511 PMC3200293 · DOI
  91. Sampol D. Ostrofet E. Jobin M. L. Raffard G. Sanchez S. Bouchaud V. (2013). Glucose and lactate metabolism in the awake and stimulated rat: a (13)C-NMR study. Front. Neuroenergetics 5: 5 10.3389/fnene.2013.00005 PMC3668265 23755012 · DOI
  92. Scharf M. T. Naidoo N. Zimmerman J. E. Pack A. I. (2008). The energy hypothesis of sleep revisited. Prog. Neurobiol. 86 264– 280 10.1016/j.pneurobio.2008.08.003 18809461 PMC2948963 · DOI
  93. Serres S. Bezancon E. Franconi J. M. Merle M. (2004). Ex vivo analysis of lactate and glucose metabolism in the rat brain under different states of depressed activity. J. Biol. Chem. 279 47881– 47889 10.1074/jbc.M409429200 15361523 · DOI
  94. Shank R. P. Bennett G. S. Freytag S. O. Campbell G. L. (1985). Pyruvate carboxylase: an astrocyte-specific enzyme implicated in the replenishment of amino acid neurotransmitter pools. Brain Res. 329 364– 367 10.1016/0006-8993(85)90552-9 3884090 · DOI
  95. Shen J. Petersen K. F. Behar K. L. Brown P. Nixon T. W. Mason G. F. (1999). Determination of the rate of the glutamate/glutamine cycle in the human brain by in vivo 13C NMR. Proc. Natl. Acad. Sci. U.S.A. 96 8235– 8240 10.1073/pnas.96.14.8235 10393978 PMC22218 · DOI · Paper page
  96. Shimizu H. Watanabe E. Hiyama T. Y. Nagakura A. Fujikawa A. Okado H. (2007). Glial Nax channels control lactate signaling to neurons for brain [Na+] sensing. Neuron 54 59– 72 10.1016/j.neuron.2007.03.014 17408578 · DOI
  97. Sibson N. R. Dhankhar A. Mason G. F. Behar K. L. Rothman D. L. Shulman R. G. (1997). In vivo 13C NMR measurements of cerebral glutamine synthesis as evidence for glutamate-glutamine cycling. Proc. Natl. Acad. Sci. U.S.A. 94 2699– 2704 10.1073/pnas.94.6.2699 9122259 PMC20152 · DOI
  98. Sibson N. R. Dhankhar A. Mason G. F. Rothman D. L. Behar K. L. Shulman R. G. (1998). Stoichiometric coupling of brain glucose metabolism and glutamatergic neuronal activity. Proc. Natl. Acad. Sci. U.S.A. 95 316– 321 10.1073/pnas.95.1.316 9419373 PMC18211 · DOI · Paper page
  99. Sibson N. R. Mason G. F. Shen J. Cline G. W. Herskovits A. Z. Wall J. E. (2001). In vivo (13)C NMR measurement of neurotransmitter glutamate cycling, anaplerosis and TCA cycle flux in rat brain during. J. Neurochem. 76 975– 989 10.1046/j.1471-4159.2001.00074.x 11181817 · DOI
  100. Somersalo E. Cheng Y. Calvetti D. (2012). The metabolism of neurons and astrocytes through mathematical models. Ann. Biomed. Eng. 40 2328– 2344 10.1007/s10439-012-0643-z 23001357 · DOI
  101. Somjen G. G. (1988). Nervenkitt: notes on the history of the concept of neuroglia. Glia 1 2– 9 10.1002/glia.440010103 2976736 · DOI
  102. Sonnewald U. Westergaard N. Hassel B. Muller T. B. Unsgard G. Fonnum F. (1993). NMR spectroscopic studies of 13C acetate and 13C glucose metabolism in neocortical astrocytes: evidence for mitochondrial heterogeneity. Dev. Neurosci. 15 351– 358 10.1159/000111355 7805589 · DOI
  103. Sorg O. Magistretti P. J. (1991). Characterization of the glycogenolysis elicited by vasoactive intestinal peptide, noradrenaline and adenosine in primary cultures of mouse cerebral cortical astrocytes. Brain Res. 563 227– 233 10.1016/0006-8993(91)91538-C 1664773 · DOI
  104. Suzuki A. Stern S. A. Bozdagi O. Huntley G. W. Walker R. H. Magistretti P. J. (2011). Astrocyte-neuron lactate transport is required for long-term memory formation. Cell 144 810– 823 10.1016/j.cell.2011.02.018 21376239 PMC3073831 · DOI · Paper page
  105. Takahashi S. Driscoll B. F. Law M. J. Sokoloff L. (1995). Role of sodium and potassium ions in regulation of glucose metabolism in cultured astroglia. Proc. Natl. Acad. Sci. U.S.A. 92 4616– 4620 10.1073/pnas.92.10.4616 7753851 PMC41995 · DOI
  106. Teixeira A. P. Santos S. S. Carinhas N. Oliveira R. Alves P. M. (2008). Combining metabolic flux analysis tools and 13C NMR to estimate intracellular fluxes of cultured astrocytes. Neurochem. Int. 52 478– 486 10.1016/j.neuint.2007.08.007 17904693 · DOI
  107. Tsacopoulos M. Evêquoz-Mercier V. Perrottet P. Buchner E. (1988). Honeybee retinal glial cells transform glucose and supply the neurons with a metabolic substrate. Proc. Natl. Acad. Sci. U.S.A. 85 8727– 8731 10.1073/pnas.85.22.8727 3186756 PMC282534 · DOI
  108. Tsacopoulos M. Veuthey A. L. Saravelos S. G. Perrottet P. Tsoupras G. (1994). Glial cells transform glucose to alanine, which fuels the neurons in the honeybee retina. J. Neurosci. 14 1339– 1351 8120629 PMC6577565
  109. Tyson R. L. Gallagher C. Sutherland G. R. (2003). 13C-Labeled substrates and the cerebral metabolic compartmentalization of acetate and lactate. Brain Res. 992 43– 52 10.1016/j.brainres.2003.08.027 14604771 · DOI
  110. Van den Berg C. J. Krzalic L. Mela P. Waelsch H. (1969). Compartmentation of glutamate metabolism in brain. Evidence for the existence of two different tricarboxylic acid cycles in brain. Biochem. J. 113 281– 290 5808317 PMC1184634
  111. Voutsinos-Porche B. Bonvento G. Tanaka K. Steiner P. Welker E. Chatton J.-Y. (2003). Glial glutamate transporters mediate a functional metabolic crosstalk between neurons and astrocytes in the mouse developing cortex. Neuron 37 275– 286 10.1016/S0896-6273(02)01170-4 12546822 · DOI
  112. Waagepetersen H. S. Bakken I. J. Larsson O. M. Sonnewald U. Schousboe A. (1998a). Comparison of lactate and glucose metabolism in cultured neocortical neurons and astrocytes using 13C-NMR spectroscopy. Dev. Neurosci. 20 310– 320 10.1159/000017326 9778567 · DOI
  113. Waagepetersen H. S. Bakken I. J. Larsson O. M. Sonnewald U. Schousboe A. (1998b). Metabolism of lactate in cultured GABAergic neurons studied by 13C nuclear magnetic resonance spectroscopy. J. Cereb. Blood Flow Metab. 18 109– 117 10.1097/00004647-199801000-00011 9428311 · DOI
  114. Walz W. Mukerji S. (1988). Lactate release from cultured astrocytes and neurons: a comparison. Glia 1 366– 370 10.1002/glia.440010603 2976396 · DOI · Paper page
  115. Waniewski R. A. Martin D. L. (1998). Preferential utilization of acetate by astrocytes is attributable to transport. J. Neurosci. 18 5225– 5233 9651205 PMC6793490
  116. Wyss M. T. Weber B. Treyer V. Heer S. Pellerin L. Magistretti P. J. (2009). Stimulation-induced increases of astrocytic oxidative metabolism in rats and humans investigated with 1-11C-acetate. J. Cereb. Blood Flow Metab. 29 44– 56 10.1038/jcbfm.2008.86 18714330 · DOI
  117. Yu A. C. Drejer J. Hertz L. Schousboe A. (1983). Pyruvate carboxylase activity in primary cultures of astrocytes and neurons. J. Neurochem. 41 1484– 1487 10.1111/j.1471-4159.1983.tb00849.x 6619879 · DOI
  118. Zwingmann C. Richter-Landsberg C. Brand A. Leibfritz D. (2000). NMR spectroscopic study on the metabolic fate of [3-(13)C]alanine in astrocytes, neurons, and cocultures: implications for glia-neuron interactions in neurotransmitter metabolism. Glia 32 286– 303 10.1002/1098-1136(200012)32:3<286::AID-GLIA80>3.0.CO;2-P 11102969 · DOI
  119. Zwingmann C. Richter-Landsberg C. Leibfritz D. (2001). 13C isotopomer analysis of glucose and alanine metabolism reveals cytosolic pyruvate compartmentation as part of energy metabolism in astrocytes. Glia 34 200– 212 10.1002/glia.1054 11329182 · DOI

Cited by

Sorted by citations

Authors
Bouzier-Sore, A.-K., & Pellerin, L.
Affiliations
University of Lausanne (CH)
Corresponding author
Pellerin, Luc
ORCID
Pellerin, Luc
Venue
Frontiers in Cellular Neuroscience
Publisher
Frontiers Media SA
Published
2013
Volume
7
Pages
179-179
ISSN
1662-5102 (ISSN-L)
DOI
10.3389/fncel.2013.00179
PMC
PMC3795301
OpenAlex
W2050226347
Cited by
134
References
6
Citations by year
2026: 4 · 2025: 2 · 2024: 4 · 2023: 8 · 2022: 5 · 2021: 15 · 2020: 12 · 2019: 9 · 2018: 9 · 2017: 17 · 2016: 10 · 2015: 18 · 2014: 20
FWCI
1.65
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Frontiers in Cellular Neuroscience (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • SERVAL (Université de Lausanne) (publishedVersion, other-oa)
  • IRIS (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
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 › Cancer Research › Cancer, Hypoxia, and Metabolism
Keywords
astrocytes, astrocyte metabolism, glutamate uptake, glutamate recycling, aerobic glycolysis, oxidative metabolism, neurometabolic coupling, glutamatergic activity, astrocyte energy metabolism

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review