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Cited by 88Neuroscience and Neuropharmacology ResearchAmino Acid Enzymes and MetabolismNeuroinflammation and Neurodegeneration Mechanisms

Aspects of Astrocyte Energy Metabolism, Amino Acid Neurotransmitter Homoeostasis and Metabolic Compartmentation

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Kreft, Marko, Bak, Lasse K, Waagepetersen, Helle S, Schousboe, Arne·2012·ASN Neuro
DOI 10.1042/an20120007PMC PMC3338196
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Abstract

Astrocytes are key players in brain function; they are intimately involved in neuronal signalling processes and their metabolism is tightly coupled to that of neurons. In the present review, we will be concerned with a discussion of aspects of astrocyte metabolism, including energy-generating pathways and amino acid homoeostasis. A discussion of the impact that uptake of neurotransmitter glutamate may have on these pathways is included along with a section on metabolic compartmentation.

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  1. Abdul Muneer PM Alikunju S Szlachetka AM Mercer AJ Haorah J Ethanol impairs glucose uptake by human astrocytes and neurons: protective effects of acetyl-l-carnitine. Int J Physiol Pathophysiol Pharmacol 2011 3 48 56 21258656 PMC3023411
  2. Allaman I Fiumelli H Magistretti PJ Martin JL Fluoxetine regulates the expression of neurotrophic/growth factors and glucose metabolism in astrocytes. Psychopharmacology (Berl) 2011 216 75 84 21301813
  3. Anderson C Bergher J Swanson R ATP-induced ATP release from astrocytes. J Neurochem 2004 88 246 256 14675168
  4. Arluison M Quignon M Nguyen P Thorens B Leloup C Penicaud L Distribution and anatomical localization of the glucose transporter 2 (GLUT2) in the adult rat brain – an immunohistochemical study. J Chem Neuroanat 2004 28 117 136 15482899
  5. Bak LK Schousboe A Waagepetersen HS The glutamate/GABA-glutamine cycle: aspects of transport, neurotransmitter homeostasis and ammonia transfer. J Neurochem 2006 98 641 653 16787421
  6. Bak LK Waagepetersen HS Melø TM Schousboe A Sonnewald U Complex glutamate labeling from [U-13C]glucose or [U-13C]lactate in co-cultures of cerebellar neurons and astrocytes. Neurochem Res 2007 32 671 680 17021949
  7. Bak LK Walls AB Schousboe A Ring A Sonnewald U Waagepetersen HS Neuronal glucose but not lactate utilization is positively correlated with NMDA-induced neurotransmission and fluctuations in cytosolic Ca2+ levels. J Neurochem 2009 109 Suppl 1 87 93 19393013
  8. Barros LF Deitmer JW Glucose and lactate supply to the synapse. Brain Res Rev 2010 63 149 159 19879896
  9. Barros LF Martinez C An enquiry into metabolite domains. Biophysical Journal 2007 92 3878 3884 17369414 PMC1868987
  10. Ben-Yoseph O Boxer P Ross B Oxidative stress in the central nervous system: monitoring the metabolic response using the pentose phosphate pathway. Dev Neurosci 1994 16 328 336 7768213
  11. Bergles D Dzubay J Jahr C Glutamate transporter currents in Bergmann glial cells follow the time course of extrasynaptic glutamate. Proc Natl Acad Sci 1997 USA.94 14821 14825 9405697 PMC25121
  12. Berl S Lajtha A Waeelsch H Amino acid and protein metabolism–IV. Cerebral compartments of glutamic acid metabolism. J Neurochem 1961 7 186 197 13642066
  13. Berl S Takagaki G Clarke DD Waelsch H Metabolic compartments in vivo. Ammonia and glutamic acid metabolism in brain and liver. J Biol Chem 1962 237 2562 2569 13867916
  14. Bittner C Loaiza A Ruminot I Larenas V Sotelo-Hitschfeld T Gutiérrez R Córdova A Valdebenito R Frommer W Barros L High resolution measurement of the glycolytic rate. Front Neuroenergetics 2010 15 26 20890447 PMC2947927
  15. Bittner CX Valdebenito R Ruminot I Loaiza A Larenas V Sotelo-Hitschfeld T Moldenhauer H San Martín A Gutiérrez R Zambrano M Barros LF Fast and reversible stimulation of astrocytic glycolysis by K+ and a delayed and persistent effect of glutamate. J Neurosci 2011 31 4709 4713 21430169 PMC6622916
  16. Bouzier AK Goodwin R de Gannes FM Valeins H Voisin P Canioni P Merle M Compartmentation of lactate and glucose metabolism in C6 glioma cells. A 13C and 1H NMR study. J Biol Chem 1998 273 27162 27169 9765235
  17. Brake A Julius D Signaling by extracellular nucleotides. Annu Rev Cell Dev Biol 1996 12 519 541 8970736
  18. Brazil DP Hemmings BA Ten years of protein kinase B signalling: a hard Akt to follow. Trends Biochem Sci 2001 26 657 664 11701324
  19. Brown A Ransom B Astrocyte glycogen and brain energy metabolism. Glia 2007 55 1263 1271 17659525
  20. Brown A Wender R Ransom B Metabolic substrates other than glucose support axon function in central white matter. J Neurosci Res 2001 66 839 843 11746409
  21. Caesar K Hashemi P Douhou A Bonvento G Boutelle MG Walls AB Lauritzen M Glutamate receptor-dependent increments in lactate, glucose and oxygen metabolism evoked in rat cerebellum in vivo. J Physiol 2008 586 1337 1349 18187464 PMC2375663
  22. Cataldo A Broadwell R Cytochemical identification of cerebral glycogen and glucose-6-phosphatase activity under normal and experimental conditions. II. Choroid plexus and ependymal epithelia, endothelia and pericytes. J Neurocytol 1986 15 511 524 3018177
  23. Catus SL Gibbs ME Sato M Summers RJ Hutchinson DS Role of β-adrenoceptors in glucose uptake in astrocytes using β-adrenoceptor knockout mice. Br J Pharmacol 2011 162 1700 1715 21138422 PMC3081115
  24. Chaudhry F Lehre K van Lookeren Campagne M Ottersen O Danbolt N Storm-Mathisen J Glutamate transporters in glial plasma membranes: highly differentiated localizations revealed by quantitative ultrastructural immunocytochemistry. Neuron 1995 15 711 720 7546749
  25. Chen Y Hertz L Noradrenaline effects on pyruvate decarboxylation: correlation with calcium signaling. J Neurosci Res 1999 58 599 606 10533052
  26. Cheng C Glover G Banker G Amara S A novel sorting motif in the glutamate transporter excitatory amino acid transporter 3 directs its targeting in Madin–Darby canine kidney cells and hippocampal neurons. J Neurosci 2002 22 10643 10652 12486157 PMC6758410
  27. Clark B Barbour B Currents evoked in Bergmann glial cells by parallel fibre stimulation in rat cerebellar slices. J Physiol 1997 502 335 350 9263914 PMC1159553
  28. Clegg JS Properties and metabolism of the aqueous cytoplasm and its boundaries. Am J Physiol 1984 246 R133 R151 6364846
  29. Contreras L Satrustegui J Calcium signaling in brain mitochondria: interplay of malate aspartate NADH shuttle and calcium uniporter/mitochondrial dehydrogenase pathways. J Biol Chem 2009 284 7091 7099 19129175 PMC2652317
  30. Cornell-Bell A Finkbeiner S Cooper M Smith S Glutamate induces calcium waves in cultured astrocytes: long-range glial signaling. Science 1990 247 470 473 1967852
  31. Cotman CW Foster A Lanthorn T An overview of glutamate as a neurotransmitter. Adv Biochem Psychopharmacol 1981 27 1 27 6108689
  32. Cotrina ML Lin JH Alves-Rodrigues A Liu S Azmi-Ghadimi H Kang J Naus CC Nedergaard M Connexins regulate calcium signaling by controlling ATP release. Proc Natl Acad Sci USA 1998 95 15735 15740 9861039 PMC28113
  33. Cross DA Alessi DR Cohen P Andjelkovich M Hemmings BA Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature 1995 378 785 789 8524413
  34. Cruz F Villalba M Garcia-Espinosa MA Ballesteros P Bogonez E Satrustegui J Cerdan S Intracellular compartmentation of pyruvate in primary cultures of cortical neurons as detected by (13)C NMR spectroscopy with multiple (13)C labels. J Neurosci Res 2001 66 771 781 11746401
  35. Danbolt N Glutamate uptake. Prog Neurobiol 2001 65 1 105 11369436
  36. Derouiche A Hertz L The perisynaptic astrocyte process as a glial compartment-immunolabelling for gluthamine synthetase and other glial markers. Nonneuronal Cells of the Nervous System 2004 Amsterdam, The Netherlands Elsevier 147 163
  37. Dienel G Lactate muscles its way into consciousness: fueling brain activation. Am J Physiol Regul Integr Comp Physiol 2004 287 R519 R521 15308501
  38. Dienel G Cruz N Astrocyte activation in working brain: energy supplied by minor substrates. Neurochem Int 2006 48 586 595 16513214
  39. DiNuzzo M Mangia S Maraviglia B Giove F Glycogenolysis in astrocytes supports blood–borne glucose channeling not glycogen-derived lactate shuttling to neurons: evidence from mathematical modeling. J Cereb Blood Flow Metab 2010 30 1895 1904 20827264 PMC3002884
  40. Drejer J Larsson OM Kvamme E Svenneby G Hertz L Schousboe A Ontogenetic development of glutamate metabolizing enzymes in cultured cerebellar granule cells and in cerebellum in vivo. Neurochem Res 1985 10 49 62 2858827
  41. Dringen R Hamprecht B Differences in glycogen metabolism in astroglia-rich primary cultures and sorbitol-selected astroglial cultures derived from mouse brain. Glia 1993 8 143 149 8225556
  42. Dzubay J Jahr C The concentration of synaptically released glutamate outside of the climbing fiber-Purkinje cell synaptic cleft. J Neurosci 1999 19 5265 5274 10377338 PMC6782308
  43. Erecinska M Silver IA Metabolism and role of glutamate in mammalian brain. Prog Neurobiol 1990 35 245 296 1980745
  44. Fehr M Lalonde S Lager I Wolff M Frommer W In vivo imaging of the dynamics of glucose uptake in the cytosol of COS-7 cells by fluorescent nanosensors. J Biol Chem 2003 278 19127 19133 12649277
  45. Fellows L Boutelle M Fillenz M Extracellular brain glucose levels reflect local neuronal activity: a microdialysis study in awake, freely moving rats. J Neurochem 1992 59 2141 2147 1431898
  46. Fillenz M Lowry J Boutelle M Fray A The role of astrocytes and noradrenaline in neuronal glucose metabolism. Acta Physiol Scand 1999 167 275 284 10632627
  47. Forsyth R Astrocytes and the delivery of glucose from plasma to neurons. Neurochem Int 1996 28 231 241 8813240
  48. Forsyth R Bartlett K Burchell A Scott H Eyre J Astrocytic glucose-6-phosphatase and the permeability of brain microsomes to glucose 6-phosphate. Biochem J 1993 294 145 151 8395816 PMC1134577
  49. Fournier K González M Robinson M Rapid trafficking of the neuronal glutamate transporter, EAAC1: evidence for distinct trafficking pathways differentially regulated by protein kinase C and platelet-derived growth factor. J Biol Chem 2004 279 34505 34513 15197183
  50. Franke H Grosche J Schädlich H Krügel U Allgaier C Illes P P2X receptor expression on astrocytes in the nucleus accumbens of rats. Neuroscience 2001 108 421 429 11738256
  51. Franke H Krügel U Grosche J Heine C Härtig W Allgaier C Illes P P2Y receptor expression on astrocytes in the nucleus accumbens of rats. Neuroscience 2004 127 431 441 15262333
  52. Fray A Forsyth R Boutelle M Fillenz M The mechanisms controlling physiologically stimulated changes in rat brain glucose and lactate: a microdialysis study. J Physiol 1996 496 49 57 8910195 PMC1160823
  53. Fujita T Williams EK Jensen TK Smith NA Takano T Tieu K Nedergaard M Cultured astrocytes do not release adenosine during hypoxic conditions. J Cereb Blood Flow Metab 2012 32 e1 e7 21989480 PMC3323303
  54. Fumagalli M Brambilla R D'Ambrosi N Volonté C Matteoli M Verderio C Abbracchio MP Nucleotide-mediated calcium signaling in rat cortical astrocytes: role of P2X and P2Y receptors. Glia 2003 43 218 203 12898701
  55. Gandhi G Cruz N Ball K Dienel G Astrocytes are poised for lactate trafficking and release from activated brain and for supply of glucose to neurons. J Neurochem 2009 111 522 536 19682206 PMC2773544
  56. Ghosh A Cheung Y Mansfield B Chou J Brain contains a functional glucose-6-phosphatase complex capable of endogenous glucose production. J Biol Chem 2005 280 11114 11119 15661744
  57. Gibbs M Hutchinson D Hertz L Astrocytic involvement in learning and memory consolidation. Neurosci Biobehav Rev 2008 32 927 944 18462796
  58. Gordon G Choi H Rungta R Ellis-Davies G MacVicar B Brain metabolism dictates the polarity of astrocyte control over arterioles. Nature 2008 456 745 749 18971930 PMC4097022
  59. Griffin L Gelb B Adams V McCabe E Developmental expression of hexokinase 1 in the rat. Biochim Biophys Acta 1992 1129 309 317 1536882
  60. Guthrie P Knappenberger J Segal M Bennett M Charles A Kater S ATP released from astrocytes mediates glial calcium waves. J Neurosci 1999 19 520 528 9880572 PMC6782195
  61. Hawkins R The blood–brain barrier and glutamate. Am J Clin Nutr 2009 90 867S 874S 19571220 PMC3136011
  62. Heni M Hennige AM Peter A Siegel-Axel D Ordelheide AM TCA N Machicao F Fritsche A Häring HU Staiger H Insulin promotes glycogen storage and cell proliferation in primary human astrocytes. PLoS ONE 2011 6 e21594 21738722 PMC3124526
  63. Hertz L Glutamate, a neurotransmitter-and so much more. A synopsis of Wierzba III. Neurochem Int 2006 48 416 425 16500003
  64. Hertz L Dienel G Energy metabolism in the brain. Int Rev Neurobiol 2002 51 1 102 12420357
  65. Hertz L Zielke H Astrocytic control of glutamatergic activity: astrocytes as stars of the show. Trends Neurosci 2004 27 735 743 15541514
  66. Hertz L Gibbs M What learning in day-old chickens can teach a neurochemist: focus on astrocyte metabolism. J Neurochem 2009 109 Suppl 1 10 16 19393003
  67. Hertz L Drejer J Schousboe A Energy metabolism in glutamatergic neurons, GABAergic neurons and astrocytes in primary cultures. Neurochem Res 1988 13 605 610 2901049
  68. Hertz L Peng L Westergaard N Yudkoff M Schousboe A Schousboe A Diemer NH Kofod H Neuronal-astrocytic interactions in metabolism of transmitter amino acids of the glutamate family. Drug Research Related to Neuroactive Amino Acids, Alfred Benzon Symposium 32 1992 Munksgaard, Copenhagen 30 48
  69. Hertz L Swanson RA Newman GC Marrif H Juurlink BH Peng L Can experimental conditions explain the discrepancy over glutamate stimulation of aerobic glycolysis? Dev Neurosci 1998 20 339 347 9778570
  70. Hertz L Peng L Dienel G Energy metabolism in astrocytes: high rate of oxidative metabolism and spatiotemporal dependence on glycolysis/glycogenolysis. J Cereb Blood Flow Metab 2007 27 219 249 16835632
  71. Hertz L Lovatt D Goldman S Nedergaard M Adrenoceptors in brain: Cellular gene expression and effects on astrocytic metabolism and [Ca(2+)](i). Neurochem Int 2010 57 411 20 20380860 PMC2934885
  72. Hollenbeck PJ Saxton WM The axonal transport of mitochondria. J Cell Sci 2005 118 5411 5419 16306220 PMC1533994
  73. Hu Y Wilson G A temporary local energy pool coupled to neuronal activity: fluctuations of extracellular lactate levels in rat brain monitored with rapid-response enzyme-based sensor. J Neurochem 1997 69 1484 1490 9326277
  74. Hutchinson DS Catus SL Merlin J Summers RJ Gibbs ME α2-Adrenoceptors activate noradrenaline-mediated glycogen turnover in chick astrocytes. J Neurochem 2011 117 915 926 21447002
  75. Huwiler A Rölz W Dorsch S Ren S Pfeilschifter J Extracellular ATP and UTP activate the protein kinase B/Akt cascade via the P2Y(2) purinoceptor in renal mesangial cells. Br J Pharmacol 2002 136 520 529 12055130 PMC1573377
  76. Ibrahim M Glycogen and its related enzymes of metabolism in the central nervous system. Adv Anat Embryol Cell Biol 1975 52 3 89 813499
  77. Innocenti B Pfeiffer S Zrenner E Kohler K Guenther E ATP-induced non-neuronal cell permeabilization in the rat inner retina. J Neurosci 2004 24 8577 8583 15456831 PMC6729894
  78. Iwabuchi S Kawahara K Inducible astrocytic glucose transporter-3 contributes to the enhanced storage of intracellular glycogen during reperfusion after ischemia. Neurochem Int 2011 59 319 325 21703319
  79. Jacques-Silva M Rodnight R Lenz G Liao Z Kong Q Tran M Kang Y Gonzalez F Weisman G Neary J P2X7 receptors stimulate AKT phosphorylation in astrocytes. Br J Pharmacol 2004 141 1106 1117 15023862 PMC1574879
  80. Jayakumar AR Rama Rao KV Schousboe A Norenberg MD Glutamine-induced free radical production in cultured astrocytes. Glia 2004 46 296 301 15048852
  81. Jayakumar DT Harris RA French S Blair PV You J Bemis KG Wang M Balaban RS Tissue heterogeneity of the mammalian mitochondrial proteome. Am J Physiol Cell Physiol 2007 292 C689 C697 16928776
  82. Kacem K Lacombe P Seylaz J Bonvento G Structural organization of the perivascular astrocyte endfeet and their relationship with the endothelial glucose transporter: a confocal microscopy study. Glia 1998 23 1 10 9562180
  83. Kasischke K Lactate fuels the neonatal brain. Front Neuroenergetics 2011 3 4 21687795 PMC3108381
  84. Kimelberg HK Nedergaard M Functions of astrocytes and their potential as therapeutic targets. Neurotherapeutics 2010 7 338 353 20880499 PMC2982258
  85. Koizumi S Fujishita K Inoue K Regulation of cell-to-cell communication mediated by astrocytic ATP in the CNS. Purinergic Signal 2005 1 211 217 18404506 PMC2096541
  86. Kovacic PB Chowdhury HH Velebit J Kreft M Jensen J Zorec R New insights into cytosolic glucose levels during differentiation of 3T3-L1 fibroblasts into adipocytes. J Biol Chem 2011 286 13370 13381 21349852 PMC3075683
  87. Kreft M Stenovec M Rupnik M Grilc S Krzan M Potokar M Pangrsic T Haydon P Zorec R Properties of Ca(2+)-dependent exocytosis in cultured astrocytes. Glia 2004 46 437 445 15095373
  88. Lai J Behar K Liang B Hertz L Hexokinase in astrocytes: kinetic and regulatory properties. Metab Brain Dis 1999 14 125 133 10488914
  89. Larsson OM Drejer J Kvamme E Svenneby G Hertz L Schousboe A Ontogenetic development of glutamate and GABA metabolizing enzymes in cultured cerebral cortex interneurons and in cerebral cortex in vivo. Int J Dev Neurosci 1985 3 177 185 24874599
  90. Leino R Gerhart D van Bueren A McCall A Drewes L Ultrastructural localization of GLUT 1 and GLUT 3 glucose transporters in rat brain. J Neurosci Res 1997 49 617 626 9302083
  91. Leloup C Arluison M Lepetit N Cartier N Marfaing-Jallat P Ferré P Pénicaud L Glucose transporter 2 (GLUT 2): expression in specific brain nuclei. Brain Res 1994 638 221 226 8199863
  92. Leo G Driscoll B Shank R Kaufman E Analysis of [1-13C]D-glucose metabolism in cultured astrocytes and neurons using nuclear magnetic resonance spectroscopy. Dev Neurosci 1993 15 282 288 7805580
  93. Liao S Chen C L-glutamate decreases glucose utilization by rat cortical astrocytes. Neurosci Lett 2003 348 81 84 12902023
  94. Lovatt D Sonnewald U Waagepetersen HS Schousboe A He W Lin JHC Han X Takano T Wang S Sim FJ Goldman SA Nedergaard M The transcriptome and metabolic gene signature of protoplasmic astrocytes in the adult murine cortex. J Neurosci 2007 47 12255 12266 17989291 PMC6673251
  95. Lynch R Fogarty K Fay F Modulation of hexokinase association with mitochondria analysed with quantitative three-dimensional confocal microscopy. J Cell Biol 1991 112 385 395 1991789 PMC2288830
  96. Martín ED Fernández M Perea G Pascual O Haydon PG Araque A Ceña V Adenosine released by astrocytes contributes to hypoxia-induced modulation of synaptic transmission. Glia 2007 55 36 45 17004232
  97. McKenna MC Sonnewald U Huang X Stevenson J Zielke HR Exogenous glutamate concentration regulates the metabolic fate of glutamate in astrocytes. J Neurochem 1996 66 386 393 8522979
  98. McKenna M Stevenson J Huang X Hopkins I Differential distribution of the enzymes glutamate dehydrogenase and aspartate aminotransferase in cortical synaptic mitochondria contributes to metabolic compartmentation in cortical synaptic terminals. Neurochem Int 2000 37 229 241 10812208
  99. McKenna MC Dienel GA Sonnewald U Waagepetersen HS Schousboe A Brady ST Siegel GJ Albers RW Price DI Energy metabolism of the brain. Basic Neurochemistry: Principles of Molecular, Cellular, and Medical Neurobiology, 8th ed 2012 Waltham, MA, USA Academic Press, Elsevier 200 231
  100. Magistretti P Regulation of glycogenolysis by neurotransmitters in the central nervous system. Diabetes Metab 1988 14 237 246 2900788
  101. Magistretti P Neuron-glia metabolic coupling and plasticity. J Exp Biol 2006 209 2304 2311 16731806
  102. Maher F Vannucci S Simpson I Glucose transporter proteins in brain. FASEB J 1994 8 1003 1011 7926364
  103. Martinez C Kalise D Barros LF General requirement for harvesting antennae at ca and h channels and transporters. Front Neuroenergetics 2010 10 27 20877432 PMC2944668
  104. Mathiisen TM Lehre KP Danbolt NC Ottersen OP The perivascular astroglial sheath provides a complete covering of the brain microvessels: an electron microscopic 3D reconstruction. Glia 2010 58 1094 1103 20468051
  105. McManus EJ Sakamoto K Armit LJ Ronaldson L Shpiro N Marquez R Alessi DR Role that phosphorylation of GSK3 plays in insulin and Wnt signalling defined by knockin analysis. EMBO J 2005 24 1571 1583 15791206 PMC1142569
  106. Medina M Castro A Glycogen synthase kinase-3 (GSK-3) inhibitors reach the clinic. Curr Opin Drug Discov Devel 2008 11 533 543 18600569
  107. Miller A Hawkins R Veech R Decreased rate of glucose utilization by rat brain in vivo after exposure to atmospheres containing high concentrations of CO2. J Neurochem 1975 25 553 558 172603
  108. Morgello S Uson R Schwartz E Haber R The human blood–brain barrier glucose transporter (GLUT1) is a glucose transporter of gray matter astrocytes. Glia 1995 14 43 54 7615345
  109. Nagamatsu S Nakamichi Y Inoue N Inoue M Nishino H Sawa H Rat C6 glioma cell growth is related to glucose transport and metabolism. Biochem J 1996 319 477 482 8912684 PMC1217793
  110. Neary J Kang Y P2 purinergic receptors signal to glycogen synthase kinase-3beta in astrocytes. J Neurosci Res 2006 84 515 524 16810687
  111. Needels D Wilson J The identity of hexokinase activities from mitochondrial and cytoplasmic fractions of rat brain homogenates. J Neurochem 1983 40 1134 1143 6834044
  112. Nie X Olsson Y Endothelin peptides in brain diseases. Rev Neurosci 1996 7 177 186 8916291
  113. Niitsu Y Hori O Yamaguchi A Bando Y Ozawa K Tamatani M Ogawa S Tohyama M Exposure of cultured primary rat astrocytes to hypoxia results in intracellular glucose depletion and induction of glycolytic enzymes. Brain Res Mol Brain Res 1999 74 26 34 10640673
  114. Norenberg MD Martinez-Hernandez A Fine structural localization of glutamine synthetase in astrocytes of rat brain. Brain Res 1979 161 303 310 31966
  115. Northam W Bedoy C Mobley P Pharmacological identification of the alpha-adrenergic receptor type which inhibits the beta-adrenergic activated adenylate cyclase system in cultured astrocytes. Glia 1989 2 129 133 2542160
  116. Obel LF Andersen KM Bak LK Scousboe A Waagepetersen HS Effects of adrenergic agents on intracellular Ca2+ homeostasis and metabolism of glucose in astrocytes with an emphasis on pyruvate carboxylation, oxidative decarboxylation and recycling: implications for glutamate neurotransmission and excitotoxicity. Neurotox Res 2012 21 405 417 22194159
  117. O'Kane R Martínez-López I DeJoseph M Viña J Hawkins R Na(+)-dependent glutamate transporters (EAAT1, EAAT2, and EAAT3) of the blood–brain barrier. A mechanism for glutamate removal. J Biol Chem 1999 274 31891 31895 10542215
  118. Pangrsic T Potokar M Haydon P Zorec R Kreft M Astrocyte swelling leads to membrane unfolding, not membrane insertion. J Neurochem 2006 99 514 523 17029603
  119. Pangrsic T Potokar M Stenovec M Kreft M Fabbretti E Nistri A Pryazhnikov E Khiroug L Giniatullin R Zorec R Exocytotic release of ATP from cultured astrocytes. J Biol Chem 2007 282 28749 28758 17627942
  120. Parpura V Zorec R Gliotransmission: exocytotic release from astrocytes. Brain Res Rev 2010 63 83 92 19948188 PMC2862866
  121. Parpura V Baker B Jeras M Zorec R Regulated exocytosis in astrocytic signal integration. Neurochem Int 2010 57 451 459 20156504 PMC2892557
  122. Pellerin L Magistretti P Food for thought: challenging the dogmas. J Cereb Blood Flow Metab 2003 23 1282 1286 14600434
  123. Pellerin L Magistretti P Neuroenergetics: calling upon astrocytes to satisfy hungry neurons. Neuroscientist 2004 10 53 62 14987448
  124. Pellerin L Stolz M Sorg O Martin J Deschepper C Magistretti P Regulation of energy metabolism by neurotransmitters in astrocytes in primary culture and in an immortalized cell line. Glia 1997 21 74 83 9298849
  125. Pellerin L Bouzier-Sore A Aubert A Serres S Merle M Costalat R Magistretti P Activity-dependent regulation of energy metabolism by astrocytes: an update. Glia 2007 55 1251 1262 17659524
  126. Plaitakis A Zaganas I Regulation of human glutamate dehydrogenases: implications for glutamate, ammonia and energy metabolism in brain. J Neurosci Res 2001 66 899 908 11746417
  127. Porras OH Ruminot I Loaiza A Barros LF Na (+)-Ca (2+) cosignaling in the stimulation of the glucose transporter GLUT1 in cultured astrocytes. Glia 2008 56 59 68 17924581
  128. Prebil M Vardjan N Jensen J Zorec R Kreft M Dynamic monitoring of cytosolic glucose in single astrocytes. Glia 2011a 59 903 913 21381116
  129. Prebil M Chowdhury HH Zorec R Kreft M Changes in cytosolic glucose level in ATP stimulated live astrocytes. Biochem Biophys Res Commun 2011b 405 308 313 21237134
  130. Qu H Faero E Jorgensen P Dale O Gisvold SE Unsgard G Sonnewald U Decreased glutamate metabolism in cultured astrocytes in the presence of thiopental. Biochem Pharmacol 1999 58 1075 1080 10509760
  131. Queiroz G Gebicke-Haerter P Schobert A Starke K von Kügelgen I Release of ATP from cultured rat astrocytes elicited by glutamate receptor activation. Neuroscience 1997 78 1203 1208 9174086
  132. Ralevic V Burnstock G Receptors for purines and pyrimidines. Pharmacol Rev 1998 50 413 492 9755289
  133. Robinson M Regulated trafficking of neurotransmitter transporters: common notes but different melodies. J Neurochem 2002 80 1 11 11796738
  134. Rothstein J Martin L Levey A Dykes-Hoberg M Jin L Wu D Nash N Kuncl R Localization of neuronal and glial glutamate transporters. Neuron 1994 13 713 725 7917301
  135. Rothstein J Dykes-Hoberg M Pardo C Bristol L Jin L Kuncl R Kanai Y Hediger M Wang Y Schielke J Welty D Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate. Neuron 1996 16 675 686 8785064
  136. Sarup A Larsson OM Schousboe A GABA transporters and GABA-transaminase as drug targets. Curr Drug Targ CNS Neurol Dis 2003 2 269 277 12871037
  137. Scheiber IF Dringen R Copper accelerates glycolytic flux in cultured astrocytes. Neurochem Res 2011 36 894 903 21318477
  138. Schmidt MM Rohwedder A Dringen R Effects of chlorinated acetates on the glutathione metabolism and on glycolysis of cultured astrocytes. Neurotox Res 2011 19 628 637 20628842
  139. Schousboe A Hertz L Svenneby G Kvamme E Phosphate activated glutaminase activity and glutamine uptake in primary cultures of astrocytes. J Neurochem 1979 32 943 950 430071
  140. Schousboe A Sonnewald U Waagepetersen HS Differential roles of alanine in GABAergic and glutamatergic neurons. Neurochem Int 2003 43 311 315 12742074
  141. Schousboe A Madsen KK White HS GABA transport inhibitors and seizure protection: the past and future. Future Med Chem 2010 3 183 187 21428813
  142. Schousboe A Sickmann HM Bak LK Schousboe I Jajo FS Faek SAA Waagepetersen HS Neuron–glia interactions in glutamatergic neurotransmission: roles of oxidative and glycolytic adenosine triphosphate as energy source. J Neurosci Res 2011 89 1926 1934 21919035
  143. Schousboe A Westergaard N Sonnewald U Petersen SB Huang R Peng L Hertz L Glutamate and glutamine metabolism and compartmentation in astrocytes. Dev Neurosci 1993 15 359 366 7805590
  144. Shulman R Hyder F Rothman D Cerebral energetics and the glycogen shunt: neurochemical basis of functional imaging. Proc Natl Acad Sci USA 2001 98 6417 6422 11344262 PMC33483
  145. Sickmann H Schousboe A Fosgerau K Waagepetersen H Compartmentation of lactate originating from glycogen and glucose in cultured astrocytes. Neurochem Res 2005 30 1295 1304 16341591
  146. Silver I Erecińska M Extracellular glucose concentration in mammalian brain: continuous monitoring of changes during increased neuronal activity and upon limitation in oxygen supply in normo-, hypo-, and hyperglycemic animals. J Neurosci 1994 14 5068 5076 8046468 PMC6577171
  147. Sonnewald U Westergaard N Hassel B Muller TB Unsgard G Fonnum F Hertz L Schousboe A Petersen SB NMR spectroscopic studies of 13C acetate and 13C glucose metabolism in neocortical astrocytes: evidence for mitochondrial heterogeneity. Dev Neurosci 1993 15 351 358 7805589
  148. Sonnewald U Westergaard N Jones P Taylor A Bachelard HS Schousboe A Metabolism of [U-13C5]glutamine in cultured astrocytes studied by NMR spectroscopy: First evidence of astrocytic pyruvate recycling. J Neurochem 1996 67 2566 2572 8931491
  149. Sonnewald U Westergaard N Schousboe A Glutamate transport and metabolism in astrocytes. Glia 1997 21 99 105 9298847
  150. Stenovec M Kreft M Grilc S Pangrsic T Zorec R EAAT2 density at the astrocyte plasma membrane and Ca(2+)-regulated exocytosis. Mol Membr Biol 2008 25 203 215 18428036
  151. Subbarao K Hertz L Effect of adrenergic agonists on glycogenolysis in primary cultures of astrocytes. Brain Res 1990a 536 220 226 2085749
  152. Subbarao K Hertz L Noradrenaline induced stimulation of oxidative metabolism in astrocytes but not in neurons in primary cultures. Brain Res 1990b 527 346 349 2253040
  153. Subbarao K Hertz L Stimulation of energy metabolism by alpha-adrenergic agonists in primary cultures of astrocytes. J Neurosci Res 1991 28 399 405 1677429
  154. Sun SH Lin LB Hung AC Kuo JS ATP-stimulated Ca2+ influx and phospholipase D activities of a rat brain-derived type-2 astrocyte cell line, RBA-2, are mediated through P2X7 receptors. J Neurochem 1999 73 334 343 10386986
  155. Swanson R Physiologic coupling of glial glycogen metabolism to neuronal activity in brain. Can J Physiol Pharmacol 1992 70 Suppl S138 144 1295664
  156. Swanson R Choi D Glial glycogen stores affect neuronal survival during glucose deprivation in vitro. J Cereb Blood Flow Metab 1993 13 162 169 8417005
  157. Swanson R Yu A Chan P Sharp F Glutamate increases glycogen content and reduces glucose utilization in primary astrocyte culture. J Neurochem 1990 54 490 496 1967630
  158. Sánchez-Alvarez R Tabernero A Medina J Endothelin-1 stimulates the translocation and upregulation of both glucose transporter and hexokinase in astrocytes: relationship with gap junctional communication. J Neurochem 2004 89 703 714 15086527
  159. Takanaga H Chaudhuri B Frommer W GLUT1 and GLUT9 as major contributors to glucose influx in HepG2 cells identified by a high sensitivity intramolecular FRET glucose sensor. Biochim Biophys Acta 2008 1778 1091 1099 18177733 PMC2315637
  160. Tsacopoulos M Magistretti P Metabolic coupling between glia and neurons. J Neurosci 1996 16 877 885 8558256 PMC6578818
  161. Van den Berg CJ Garfinkel D A simulation study of brain compartments: metabolism of glutamate and related substances in mouse brain. Biochem J 1971 23 211 218 5164952 PMC1176925
  162. Vendelin M Birkedal R Anisotropic diffusion of fluorescently labeled ATP in rat cardiomyocytes determined by raster image correlation spectroscopy. Am J Physiol Cell Physiol 2008 295 C1302 C1315 18815224 PMC2584976
  163. Verderio C Matteoli M ATP mediates calcium signaling between astrocytes and microglial cells: modulation by IFN-gamma. J Immunol 2001 166 6383 6391 11342663
  164. Vesce S Bezzi P Volterra A The active role of astrocytes in synaptic transmission. Cell Mol Life Sci 1999 56 991 1000 11212330 PMC11146931
  165. Villa-Moruzzi E Locci-Cubeddu T Bergamini E Effects of adrenaline administration on the activity of glycogen metabolizing enzymes in different muscle types. Pflugers Arch 1979 379 301 302 111217
  166. Waagepetersen HS Hansen GH Fenger K Lindsay JG Gibson G Schousboe A Cellular mitochondrial heterogeneity in cultured astrocytes as demonstrated by immunogold labeling of alpha-ketoglutarate dehydrogenase. Glia 2006 53 225 231 16206171
  167. Waagepetersen HS Schousboe A Squire L Albright T Bloom F Gage F Spitzer N Glial GABA and glutamate metabolism. New Enclyclopedia in Neuroscience 2007 Oxford, UK Elsevier Ltd
  168. Waagepetersen HS Sonnewald U Schousboe A Parpura V Haydon PG Energy and amino acid neurotransmitter metabolism in astrocytes. Astrocytes in (patho)physiology of the nervous system 2009 Berlin, Germany Springer 177 199
  169. Waagepetersen HS Sonnewald U Larsson OM Schousboe A A possible role of alanine for ammonia transfer between astrocytes and glutamatergic neurons. J Neurochem 2000 75 471 479 10899921
  170. Waagepetersen HS Sonnewald U Larsson OM Schousboe A Multiple compartments with different metabolic characteristics are involved in biosynthesis of intracellular and released glutamine and citrate in astrocytes. Glia 2001 35 246 252 11494415
  171. Waagepetersen HS Qu H Hertz L Sonnewald U Schousboe A Demonstration of pyruvate recycling in primary cultures of neocortical astrocytes but not in neurons. Neurochem Res 2002 27 1431 1437 12512946
  172. Walls A Heimbürger C Bouman S Schousboe A Waagepetersen H Robust glycogen shunt activity in astrocytes: Effects of glutamatergic and adrenergic agents. Neuroscience 2009 158 284 292 19000744
  173. Wang Z Haydon P Yeung E Direct observation of calcium-independent intercellular ATP signaling in astrocytes. Anal Chem 2000 72 2001 2007 10815957
  174. Wender R Brown A Fern R Swanson R Farrell K Ransom B Astrocytic glycogen influences axon function and survival during glucose deprivation in central white matter. J Neurosci 2000 20 6804 6810 10995824 PMC6772835
  175. Westergaard N Sonnewald U Schousboe A Metabolic trafficking between neurons and astrocytes: the glutamate/glutamine cycle revisited. Dev Neurosci 1995 17 203 211 8575339
  176. Westergaard N Drejer J Schousboe A Sonnewald U Evaluation of the importance of transamination versus deamination in astrocytic metabolism of [U-13C]glutamate. Glia 1996 17 160 168 8776582
  177. Wiesinger H Hamprecht B Dringen R Metabolic pathways for glucose in astrocytes. Glia 1997 21 22 34 9298844
  178. Yu A Drejer J Hertz L Schousboe A Pyruvate carboxylase activity in primary cultures of astrocytes and neurons. J Neurochem 1983 41 1484 1487 6619879
  179. Yu A Schousboe A Hertz L Metabolic fate of 14C-labeled glutamate in astrocytes in primary cultures. J Neurochem 1982 39 954 960 6126524
  180. Yu N Martin J Stella N Magistretti P Arachidonic acid stimulates glucose uptake in cerebral cortical astrocytes. Proc Natl Acad Sci USA 1993 90 4042 4046 8483920 PMC46442
  181. Zhang J Wang H Ye C Ge W Chen Y Jiang Z Wu C Poo M Duan S ATP released by astrocytes mediates glutamatergic activity-dependent heterosynaptic suppression. Neuron 2003 40 971 982 14659095
  182. Zielke HR Zielke CL Baab PJ Tildon JT Effect of fluorocitrate on cerebral oxidation of lactate and glucose in freely moving rats. J Neurochem 2007 101 9 16 17241122
  183. Zielke H Collins RJ Baab P Huang Y Zielke C Tildon J Compartmentation of [14C]glutamate and [14C]glutamine oxidative metabolism in the rat hippocampus as determined by microdialysis. J Neurochem 1998 71 1315 1320 9721758
  184. Zwingmann C Richter-Landsberg C Leibfritz D 13C isotopomer analysis of glucose and alanine metabolism reveals cytosolic pyruvate compartmentation as part of energy metabolism in astrocytes. Glia 2001 34 200 212 11329182

Cited by

Sorted by citations

Authors
Kreft, M., Bak, L. K., Waagepetersen, H. S., & Schousboe, A.
Affiliations
  • University of Ljubljana (SI)
  • University of Copenhagen (DK)
Corresponding author
Schousboe, Arne
ORCID
Venue
ASN Neuro
Publisher
Informa UK Limited
Published
2012-03
Volume
4
Issue
3
ISSN
1759-0914 (ISSN-L)
DOI
10.1042/an20120007
PMC
PMC3338196
OpenAlex
W1994015846
Cited by
88
References
8
Citations by year
2026: 4 · 2025: 6 · 2024: 4 · 2023: 4 · 2022: 3 · 2021: 11 · 2020: 4 · 2019: 5 · 2018: 4 · 2017: 7 · 2016: 9 · 2015: 6 · 2014: 7 · 2013: 12 · 2012: 2
FWCI
0.92
Type
journal article
Language
en
Open access
Licence
Locations
  • ASN NEURO (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Research at the University of Copenhagen (University of Copenhagen) (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, astrocyte energy metabolism, metabolic compartmentation, glutamate uptake, astrocyte-neuron metabolic coupling
MeSH terms
Animals, Astrocytes, Cell Compartmentation, Energy Metabolism, Homeostasis, Humans, Signal Transduction, Neurotransmitter Agents, Glutamic Acid

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