Aspects of astrocyte energy metabolism, amino acid neurotransmitter homoeostasis and metabolic compartmentation

ASN Neuro

Volumn 4, Issue 3, 2012, Pages 187-199

  Kreft, Marko ^a   Bak, Lasse K ^b   Waagepetersen, Helle S ^b   Schousboe, Arne ^b  

^a Celica Biomedical Sciences Center   (Slovenia)

^b UNIVERSITY OF COPENHAGEN   (Denmark)

Author keywords

Amino acid; Astrocyte; Compartmentation; Energy; Metabolism

Indexed keywords

ADENOSINE TRIPHOSPHATE; ADRENALIN; AMINO ACID; AMINO ACID RECEPTOR AFFECTING AGENT; GLUTAMIC ACID; GLYCOGEN; NORADRENALIN; AGENTS INTERACTING WITH TRANSMITTER, HORMONE OR DRUG RECEPTORS;

AMINO ACID METABOLISM; AMINO ACID TRANSPORT; ASTROCYTE; BRAIN METABOLISM; CELL COMPARTMENTALIZATION; CELL METABOLISM; ENERGY METABOLISM; GLUCOSE METABOLISM; GLUCOSE TRANSPORT; GLUTAMATE TRANSPORT; GLYCOGEN METABOLISM; GLYCOLYSIS; METABOLIC REGULATION; MITOCHONDRIAL RESPIRATION; NERVE CELL NECROSIS; NEUROTRANSMISSION; NEUROTRANSMITTER UPTAKE; NONHUMAN; PHOSPHORYLATION; PROTEIN HOMEOSTASIS; REVIEW; ANIMAL; HOMEOSTASIS; HUMAN; METABOLISM; PHYSIOLOGY; SIGNAL TRANSDUCTION;

ANIMALS; ASTROCYTES; CELL COMPARTMENTATION; ENERGY METABOLISM; GLUTAMIC ACID; HOMEOSTASIS; HUMANS; NEUROTRANSMITTER AGENTS; SIGNAL TRANSDUCTION;

EID: 84860599501     PISSN: None     EISSN: 17590914     Source Type: Journal    
DOI: 10.1042/AN20120007     Document Type: Review

References (194)

1. Abdul Muneer PM, Alikunju S, Szlachetka AM, Mercer AJ, Haorah J (2011) Ethanol impairs glucose uptake by human astrocytes and neurons: protective effects of acetyl-L-carnitine. Int J Physiol Pathophysiol Pharmacol 3:48-56.
2. Allaman I, Fiumelli H, Magistretti PJ, Martin JL (2011) Fluoxetine regulates the expression of neurotrophic/growth factors and glucose metabolism in astrocytes. Psychopharmacology (Berl) 216:75-84.
3. Allen N, Barres B (2009) Neuroscience: glia-more than just brain glue. Nature 457:675-677.
4. Anderson C, Bergher J, Swanson R (2004) ATP-induced ATP release from astrocytes. J Neurochem 88:246-256.
5. Arluison M, Quignon M, Nguyen P, Thorens B, Leloup C, Penicaud L (2004) Distribution and anatomical localization of the glucose transporter 2 (GLUT2) in the adult rat brain - an immunohistochemical study. J Chem Neuroanat 28:117-136.
6. Bak LK, Schousboe A, Waagepetersen HS (2006) The glutamate/GABAglutamine cycle: aspects of transport, neurotransmitter homeostasis and ammonia transfer. J Neurochem 98:641-653.
7. 13C]lactate in cocultures of cerebellar neurons and astrocytes. Neurochem Res 32:671-680.
8. 2+ levels. J Neurochem 109(Suppl 1):87-93.
9. Barros LF, Deitmer JW (2010) Glucose and lactate supply to the synapse. Brain Res Rev 63:149-159.
10. Barros LF, Martinez C (2007) An enquiry into metabolite domains. Biophysical Journal 92:3878-3884.
11. Ben-Yoseph O, Boxer P, Ross B (1994) Oxidative stress in the central nervous system: monitoring the metabolic response using the pentose phosphate pathway. Dev Neurosci 16:328-336.
12. Bergles D, Dzubay J, Jahr C (1997) Glutamate transporter currents in Bergmann glial cells follow the time course of extrasynaptic glutamate. Proc Natl Acad Sci USA.94:14821-14825.
13. Berl S, Lajtha A, Waeelsch H (1961) Amino acid and protein metabolism-IV. Cerebral compartments of glutamic acid metabolism. J Neurochem 7:186-197.
14. Berl S, Takagaki G, Clarke DD, Waelsch H (1962) Metabolic compartments in vivo. Ammonia and glutamic acid metabolism in brain and liver. J Biol Chem 237:2562-2569.
15. Bittner C, Loaiza A, Ruminot I, Larenas V, Sotelo-Hitschfeld T, Gutiérrez R, Córdova A, Valdebenito R, Frommer W, Barros L (2010) High resolution measurement of the glycolytic rate. Front Neuroenergetics 15: 26.
16. + and a delayed and persistent effect of glutamate. J Neurosci 31:4709-4713.
17. 1H NMR study. J Biol Chem 273:27162-27169.
18. Brake A, Julius D (1996) Signaling by extracellular nucleotides. Annu Rev Cell Dev Biol 12:519-541.
19. Brazil DP, Hemmings BA (2001) Ten years of protein kinase B signalling: a hard Akt to follow. Trends Biochem Sci 26:657-664.
20. Brown AM, Prior MJW (2006) Neuronal lactate metabolism-the first piece of the jigsaw falls in to place. Physiol News 64: 23-25.
21. Brown A, Ransom B (2007) Astrocyte glycogen and brain energy metabolism. Glia 55:1263-1271.
22. Brown A, Wender R, Ransom B (2001) Metabolic substrates other than glucose support axon function in central white matter. J Neurosci Res 66:839-843.
23. Caesar K, Hashemi P, Douhou A, Bonvento G, Boutelle MG, Walls AB, Lauritzen M (2008) Glutamate receptor-dependent increments in lactate, glucose and oxygen metabolism evoked in rat cerebellum in vivo. J Physiol. 586:1337-1349.
24. Cataldo A, Broadwell R (1986) 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 15:511-524.
25. Catus SL, Gibbs ME, Sato M, Summers RJ, Hutchinson DS (2011) Role of βadrenoceptors in glucose uptake in astrocytes using β-adrenoceptor knockout mice. Br J Pharmacol 162:1700-1715.
26. Chaudhry F, Lehre K, van Lookeren Campagne M, Ottersen O, Danbolt N, Storm-Mathisen J (1995) Glutamate transporters in glial plasma membranes: highly differentiated localizations revealed by quantitative ultrastructural immunocytochemistry. Neuron 15:711-720.
27. Chen Y, Hertz L (1999) Noradrenaline effects on pyruvate decarboxylation: correlation with calcium signaling. J Neurosci Res 58:599-606.
28. Cheng C, Glover G, Banker G, Amara S (2002) 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 22:10643-10652.
29. Chuquet J, Quilichini P, Nimchinsky EA, Buzsaki G (2010) Predominant enhancement of glucose uptake in astrocytes versus neurons during activation of the somatosensory cortex. J Neurosci 30:15298-15303.
30. Clark B, Barbour B (1997) Currents evoked in Bergmann glial cells by parallel fibre stimulation in rat cerebellar slices. J Physiol 502:335-350.
31. Clegg JS (1984) Properties and metabolism of the aqueous cytoplasm and its boundaries. Am J Physiol 246:R133-R151.
32. Contreras L, Satrustegui J (2009) Calcium signaling in brain mitochondria: interplay of malate aspartate NADH shuttle and calcium uniporter/ mitochondrial dehydrogenase pathways. J Biol Chem 284:7091-7099.
33. Cornell-Bell A, Finkbeiner S, Cooper M, Smith S (1990) Glutamate induces calcium waves in cultured astrocytes: long-range glial signaling. Science 247:470-473.
34. Cotman CW, Foster A, Lanthorn T (1981) An overview of glutamate as a neurotransmitter. Adv Biochem Psychopharmacol 27:1-27.
35. Cotrina ML, Lin JH, Alves-Rodrigues A, Liu S, Azmi-Ghadimi H, Kang J, Naus CC, Nedergaard M (1998) Connexins regulate calcium signaling by controlling ATP release. Proc Natl Acad Sci USA. 95:15735-15740.
36. Cross DA, Alessi DR, Cohen P, Andjelkovich M, Hemmings BA (1995) Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature 378:785-789.
37. Cruz F, Villalba M, Garcia-Espinosa MA, Ballesteros P, Bogonez E, Satrustegui J, Cerdan S (2001) 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 66:771-781.
38. Danbolt N (2001) Glutamate uptake. Prog Neurobiol 65:1-105.
39. Derouiche A (2004) The perisynaptic astrocyte process as a glial compartment-immunolabelling for gluthamine synthetase and other glial markers. In: Nonneuronal Cells of the Nervous System (Hertz L, ed.), pp 147-163. Elsevier, Amsterdam, The Netherlands.
40. Dienel G (2004) Lactate muscles its way into consciousness: fueling brain activation. Am J Physiol Regul Integr Comp Physiol 287:R519-R521.
41. Dienel G, Cruz N (2006) Astrocyte activation in working brain: energy supplied by minor substrates. Neurochem Int 48:586-595.
42. DiNuzzo M, Mangia S, Maraviglia B, Giove F (2010). Glycogenolysis in astrocytes supports blood-borne glucose channeling not glycogenderived lactate shuttling to neurons: evidence from mathematical modeling. J Cereb Blood Flow Metab 30:1895-1904.
43. DiNuzzo M, Maraviglia B, Giove F (2011) Why does the brain (not) have glycogen? Bioessays 33:319-326.
44. Drejer J, Larsson OM, Kvamme E, Svenneby G, Hertz L, Schousboe A (1985) Ontogenetic development of glutamate metabolizing enzymes in cultured cerebellar granule cells and in cerebellum in vivo. Neurochem Res 10:49-62.
45. Dringen R, Hamprecht B (1993) Differences in glycogen metabolism in astroglia-rich primary cultures and sorbitol-selected astroglial cultures derived from mouse brain. Glia 8:143-149.
46. Dzubay J, Jahr C (1999) The concentration of synaptically released glutamate outside of the climbing fiber-Purkinje cell synaptic cleft. J Neurosci 19:5265-5274.
47. Erecinska M, Silver IA (1990) Metabolism and role of glutamate in mammalian brain. Prog Neurobiol 35:245-296.
48. Fehr M, Lalonde S, Lager I, Wolff M, Frommer W (2003) In vivo imaging of the dynamics of glucose uptake in the cytosol of COS-7 cells by fluorescent nanosensors. J Biol Chem 278:19127-19133.
49. Fellows L, Boutelle M, Fillenz M (1992) Extracellular brain glucose levels reflect local neuronal activity: a microdialysis study in awake, freely moving rats. J Neurochem 59:2141-2147.
50. Fillenz M, Lowry J, Boutelle M, Fray A (1999) The role of astrocytes and noradrenaline in neuronal glucose metabolism. Acta Physiol Scand 167:275-284.
51. Forsyth R (1996) Astrocytes and the delivery of glucose from plasma to neurons. Neurochem Int 28:231-241.
52. Forsyth R, Bartlett K, Burchell A, Scott H, Eyre J (1993) Astrocytic glucose-6- phosphatase and the permeability of brain microsomes to glucose 6- phosphate. Biochem J 294:145-151.
53. Fournier K, González M, Robinson M (2004) 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 279:34505-34513.
54. Fox P, Raichle M, Mintun M, Dence C (1988) Nonoxidative glucose consumption during focal physiologic neural activity. Science 241:462-464.
55. Franke H, Grosche J, Schädlich H, Krügel U, Allgaier C, Illes P (2001) P2X receptor expression on astrocytes in the nucleus accumbens of rats. Neuroscience 108:421-429.
56. Franke H, Krügel U, Grosche J, Heine C, Härtig W, Allgaier C, Illes P (2004) P2Y receptor expression on astrocytes in the nucleus accumbens of rats. Neuroscience 127:431-441.
57. Fray A, Forsyth R, Boutelle M, Fillenz M (1996) The mechanisms controlling physiologically stimulated changes in rat brain glucose and lactate: a microdialysis study. J Physiol 496:49-57.
58. Fujita T, Williams EK, Jensen TK, Smith NA, Takano T, Tieu K, Nedergaard M. (2012) Cultured astrocytes do not release adenosine during hypoxic conditions. J Cereb Blood Flow Metab 32:e1-e7.
59. Fumagalli M, Brambilla R, D'Ambrosi N, Volonté C, Matteoli M, Verderio C, Abbracchio MP (2003) Nucleotide-mediated calcium signaling in rat cortical astrocytes: role of P2X and P2Y receptors. Glia 43:218-203.
60. Gandhi G, Cruz N, Ball K, Dienel G (2009) Astrocytes are poised for lactate trafficking and release from activated brain and for supply of glucose to neurons. J Neurochem 111:522-536.
61. Ghosh A, Cheung Y, Mansfield B, Chou J (2005) Brain contains a functional glucose-6-phosphatase complex capable of endogenous glucose production. J Biol Chem 280:11114-11119.
62. Gibbs M, Hutchinson D, Hertz L (2008) Astrocytic involvement in learning and memory consolidation. Neurosci Biobehav Rev 32:927-944.
63. Gordon G, Choi H, Rungta R, Ellis-Davies G, MacVicar B (2008) Brain metabolism dictates the polarity of astrocyte control over arterioles. Nature 456:745-749.
64. Griffin L, Gelb B, Adams V, McCabe E (1992) Developmental expression of hexokinase 1 in the rat. Biochim Biophys Acta 1129:309-317.
65. Guthrie P, Knappenberger J, Segal M, Bennett M, Charles A, Kater S (1999) ATP released from astrocytes mediates glial calcium waves. J Neurosci 19:520-528.
66. Hawkins R (2009) The blood-brain barrier and glutamate. Am J Clin Nutr 90:867S-874S.
67. Heni M, Hennige AM, Peter A, Siegel-Axel D, Ordelheide AM, TCA N, Machicao F, Fritsche A, Häring HU, Staiger H (2011) Insulin promotes glycogen storage and cell proliferation in primary human astrocytes. PLoS ONE 6:e21594.
68. Hertz L (2006) Glutamate, a neurotransmitter-and so much more. A synopsis of Wierzba III. Neurochem Int 48:416-425.
69. Hertz L, Dienel G (2002) Energy metabolism in the brain. Int Rev Neurobiol 51:1-102.
70. Hertz L, Zielke H (2004) Astrocytic control of glutamatergic activity: astrocytes as stars of the show. Trends Neurosci 27:735-743.
71. Hertz L, Gibbs M (2009) What learning in day-old chickens can teach a neurochemist: focus on astrocyte metabolism. J Neurochem 109 Suppl 1:10-16.
72. Hertz L, Drejer J, Schousboe A (1988) Energy metabolism in glutamatergic neurons, GABAergic neurons and astrocytes in primary cultures.Neurochem Res 13:605-610.
73. Hertz L, Peng L, Westergaard N, Yudkoff M, Schousboe A (1992) Neuronalastrocytic interactions in metabolism of transmitter amino acids of the glutamate family. In: Drug Research Related to Neuroactive Amino Acids, Alfred Benzon Symposium 32 (Schousboe A, Diemer NH, Kofod H, eds), pp. 30-48. Munksgaard, Copenhagen.
74. Hertz L, Swanson RA, Newman GC, Marrif H, Juurlink BH, Peng L (1998) Can experimental conditions explain the discrepancy over glutamate stimulation of aerobic glycolysis? Dev Neurosci 20:339-347.
75. Hertz L, Peng L, Dienel G (2007) Energy metabolism in astrocytes: high rate of oxidative metabolism and spatiotemporal dependence on glycolysis/ glycogenolysis. J Cereb Blood Flow Metab 27:219-249.
76. Hertz L, Lovatt D, Goldman S, Nedergaard M (2010) Adrenoceptors in brain: Cellular gene expression and effects on astrocytic metabolism and [Ca(2+)](i). Neurochem Int 57:411-20.
77. Hollenbeck PJ, Saxton WM (2005) The axonal transport of mitochondria. J Cell Sci 118:5411-5419.
78. Hu Y, Wilson G (1997) 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 69:1484-1490.
79. 2- Adrenoceptors activate noradrenaline-mediated glycogen turnover in chick astrocytes. J Neurochem 117:915-926.
80. Huwiler A, Rölz W, Dorsch S, Ren S, Pfeilschifter J (2002) Extracellular ATP and UTP activate the protein kinase B/Akt cascade via the P2Y(2) purinoceptor in renal mesangial cells. Br J Pharmacol 136:520-529.
81. Ibrahim M (1975) Glycogen and its related enzymes of metabolism in the central nervous system. Adv Anat Embryol Cell Biol 52:3-89.
82. Innocenti B, Pfeiffer S, Zrenner E, Kohler K, Guenther E (2004) ATP-induced non-neuronal cell permeabilization in the rat inner retina. J Neurosci 24:8577-8583.
83. Iwabuchi S, Kawahara K (2011) Inducible astrocytic glucose transporter-3 contributes to the enhanced storage of intracellular glycogen during reperfusion after ischemia. Neurochem Int 59:319-325.
84. Jacques-Silva M, Rodnight R, Lenz G, Liao Z, Kong Q, Tran M, Kang Y, Gonzalez F, Weisman G, Neary J (2004) P2×7 receptors stimulate AKT phosphorylation in astrocytes. Br J Pharmacol 141:1106-1117.
85. Jayakumar AR, Rama Rao KV, Schousboe A, Norenberg MD (2004) Glutamineinduced free radical production in cultured astrocytes. Glia 46:296-301.
86. Jayakumar DT, Harris RA, French S, Blair PV, You J, Bemis KG, Wang M, Balaban RS (2007) Tissue heterogeneity of the mammalian mitochondrial proteome. Am J Physiol Cell Physiol 292:C689-C697.
87. 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.
88. Kasischke K. (2011) Lactate fuels the neonatal brain. Front Neuroenergetics 3:4.
89. Kimelberg HK and Nedergaard M (2010) Functions of astrocytes and their potential as therapeutic targets. Neurotherapeutics 7:338-353.
90. Koizumi S, Fujishita K, Inoue K (2005) Regulation of cell-to-cell communication mediated by astrocytic ATP in the CNS. Purinergic Signal 1:211-217.
91. Kovacic PB, Chowdhury HH, Velebit J, Kreft M, Jensen J, Zorec R (2011) New insights into cytosolic glucose levels during differentiation of 3T3-L1 fibroblasts into adipocytes. J Biol Chem 286:13370-13381.
92. Kreft M, Stenovec M, Rupnik M, Grilc S, Krzan M, Potokar M, Pangrsic T, Haydon P, Zorec R (2004) Properties of Ca(2+)-dependent exocytosis in cultured astrocytes. Glia 46:437-445.
93. Lai J, Behar K, Liang B, Hertz L (1999) Hexokinase in astrocytes: kinetic and regulatory properties. Metab Brain Dis 14:125-133.
94. Larsson OM, Drejer J, Kvamme E, Svenneby G, Hertz L, Schousboe A (1985) Ontogenetic development of glutamate and GABA metabolizing enzymes in cultured cerebral cortex interneurons and in cerebral cortex in vivo. Int J Dev Neurosci 3:177-185.
95. Lawrence JC, Roach PJ (1997) New insights into the role and mechanism of glycogen synthase activation by insulin. Diabetes 46:541-547.
96. Leino R, Gerhart D, van Bueren A, McCall A, Drewes L (1997) Ultrastructural localization of GLUT 1 and GLUT 3 glucose transporters in rat brain. J Neurosci Res 49:617-626.
97. Leloup C, Arluison M, Lepetit N, Cartier N, Marfaing-Jallat P, Ferre ́ P, Pénicaud L (1994) Glucose transporter 2 (GLUT 2): expression in specific brain nuclei. Brain Res 638:221-226.
98. 13C]D-glucose metabolism in cultured astrocytes and neurons using nuclear magnetic resonance spectroscopy. Dev Neurosci 15:282-288.
99. Liao S, Chen C (2003) L-glutamate decreases glucose utilization by rat cortical astrocytes. Neurosci Lett 348:81-84.
100. Lieth E, LaNoue KF, Berkich DA, Xu B, Ratz M, Taylor C, Hutson SM (2001) Nitrogen shuttling between neurons and glial cells during glutamate synthesis. J Neurochem 76:1712-1723.
101. Loaiza A, Porras O, Barros L (2003) Glutamate triggers rapid glucose transport stimulation in astrocytes as evidenced by real-time confocal microscopy.J Neurosci 23:7337-7342.
102. Lovatt D, Sonnewald U, Waagepetersen HS, Schousboe A, He W, Lin JH-C, Han X, Takano T, Wang S, Sim FJ, Goldman SA, Nedergaard M (2007) The transcriptome and metabolic gene signature of protoplasmic astrocytes in the adult murine cortex. J Neurosci 47:12255-12266.
103. Lynch R, Fogarty K, Fay F (1991) Modulation of hexokinase association with mitochondria analysed with quantitative three-dimensional confocal microscopy. J Cell Biol 112:385-395.
104. Martín ED, Fernández M, Perea G, Pascual O, Haydon PG, Araque A, Ceña V. (2007) Adenosine released by astrocytes contributes to hypoxia-induced modulation of synaptic transmission. Glia 55:36-45.
105. McKenna MC, Sonnewald U, Huang X, Stevenson J, Zielke HR (1996) Exogenous glutamate concentration regulates the metabolic fate of glutamate in astrocytes. J Neurochem 66:386-393.
106. McKenna M, Stevenson J, Huang X, Hopkins I (2000) Differential distribution of the enzymes glutamate dehydrogenase and aspartate aminotransferase in cortical synaptic mitochondria contributes to metabolic compartmentation in cortical synaptic terminals. Neurochem Int 37:229-241.
107. McKenna MC, Dienel GA, Sonnewald U, Waagepetersen HS, Schousboe A (2012) Energy metabolism of the brain. In: Basic Neurochemistry: Principles of Molecular, Cellular, and Medical Neurobiology, 8th ed (Brady ST, Siegel GJ, Albers RW, Price DI, eds), pp. 200-231, Academic Press, Elsevier, Waltham, MA, USA.
108. Magistretti P (1988) Regulation of glycogenolysis by neurotransmitters in the central nervous system. Diabetes Metab 14:237-246.
109. Magistretti P (2006) Neuron-glia metabolic coupling and plasticity. J Exp Biol 209:2304-2311.
110. Maher F, Vannucci S, Simpson I (1994) Glucose transporter proteins in brain.FASEB J 8:1003-1011.
111. Martinez C, Kalise D, Barros LF (2010) General requirement for harvesting antennae at ca and h channels and transporters. Front Neuroenergetics 10: 27.
112. Mathiisen TM, Lehre KP, Danbolt NC, Ottersen OP (2010) The perivascular astroglial sheath provides a complete covering of the brain microvessels: an electron microscopic 3D reconstruction. Glia 58:1094-1103.
113. McManus EJ, Sakamoto K, Armit LJ, Ronaldson L, Shpiro N, Marquez R, Alessi DR (2005) Role that phosphorylation of GSK3 plays in insulin and Wnt signalling defined by knockin analysis. EMBO J 24:1571-1583.
114. Medina M, Castro A (2008) Glycogen synthase kinase-3 (GSK-3) inhibitors reach the clinic. Curr Opin Drug Discov Devel 11:533-543.
115. 2. J Neurochem 25:553-558.
116. Morgello S, Uson R, Schwartz E, Haber R (1995) The human blood-brain barrier glucose transporter (GLUT1) is a glucose transporter of gray matter astrocytes. Glia 14:43-54.
117. Nagamatsu S, Nakamichi Y, Inoue N, Inoue M, Nishino H, Sawa H (1996) Rat C6 glioma cell growth is related to glucose transport and metabolism. Biochem J 319:477-482.
118. Neary J, Kang Y (2006) P2 purinergic receptors signal to glycogen synthase kinase-3beta in astrocytes. J Neurosci Res 84:515-524.
119. Needels D, Wilson J (1983) The identity of hexokinase activities from mitochondrial and cytoplasmic fractions of rat brain homogenates. J Neurochem 40:1134-1143.
120. Nie X, Olsson Y (1996) Endothelin peptides in brain diseases. Rev Neurosci 7:177-186.
121. Niitsu Y, Hori O, Yamaguchi A, Bando Y, Ozawa K, Tamatani M, Ogawa S, Tohyama M (1999) Exposure of cultured primary rat astrocytes to hypoxia results in intracellular glucose depletion and induction of glycolytic enzymes. Brain Res Mol Brain Res 74:26-34.
122. Norenberg MD, Martinez-Hernandez A (1979) Fine structural localization of glutamine synthetase in astrocytes of rat brain. Brain Res 161:303-310.
123. Northam W, Bedoy C, Mobley P (1989) Pharmacological identification of the alpha-adrenergic receptor type which inhibits the beta-adrenergic activated adenylate cyclase system in cultured astrocytes. Glia 2:129- 133.
124. 2+ 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 21:405-417.
125. O'Kane R, Martínez-López I, DeJoseph M, Viña J, Hawkins R (1999) Na(+)- dependent glutamate transporters (EAAT1, EAAT2, and EAAT3) of the blood-brain barrier. A mechanism for glutamate removal. J Biol Chem 274:31891-31895.
126. Pangrsic T, Potokar M, Haydon P, Zorec R, Kreft M (2006) Astrocyte swelling leads to membrane unfolding, not membrane insertion. J Neurochem 99:514-523.
127. Pangrsic T, Potokar M, Stenovec M, Kreft M, Fabbretti E, Nistri A, Pryazhnikov E, Khiroug L, Giniatullin R, Zorec R (2007) Exocytotic release of ATP from cultured astrocytes. J Biol Chem 282:28749-28758.
128. Parpura V, Zorec R (2010) Gliotransmission: exocytotic release from astrocytes. Brain Res Rev 63:83-92.
129. Parpura V, Baker B, Jeras M, Zorec R (2010) Regulated exocytosis in astrocytic signal integration. Neurochem Int 57:451-459.
130. Pellerin L, Magistretti P (1994) Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc Natl Acad Sci USA. 91:10625-10629.
131. Pellerin L, Magistretti P (2003) Food for thought: challenging the dogmas. J Cereb Blood Flow Metab 23:1282-1286.
132. Pellerin L, Magistretti P (2004) Neuroenergetics: calling upon astrocytes to satisfy hungry neurons. Neuroscientist 10:53-62.
133. Pellerin L, Stolz M, Sorg O, Martin J, Deschepper C, Magistretti P (1997) Regulation of energy metabolism by neurotransmitters in astrocytes in primary culture and in an immortalized cell line. Glia 21:74-83.
134. Pellerin L, Bouzier-Sore A, Aubert A, Serres S, Merle M, Costalat R, Magistretti P (2007) Activity-dependent regulation of energy metabolism by astrocytes: an update. Glia 55:1251-1262.
135. Plaitakis A, Zaganas I (2001) Regulation of human glutamate dehydrogenases: implications for glutamate, ammonia and energy metabolism in brain. J Neurosci Res 66:899-908.
136. Porras OH, Ruminot I, Loaiza A, Barros LF (2008) Na (+)-Ca (2+) cosignaling in the stimulation of the glucose transporter GLUT1 in cultured astrocytes. Glia 56:59-68.
137. Prebil M, Vardjan N, Jensen J, Zorec R, Kreft M (2011a) Dynamic monitoring of cytosolic glucose in single astrocytes. Glia 59: 903-913.
138. Prebil M, Chowdhury HH, Zorec R, Kreft M (2011b) Changes in cytosolic glucose level in ATP stimulated live astrocytes. Biochem Biophys Res Commun 405:308-313.
139. Qu H, Faero E, Jorgensen P, Dale O, Gisvold SE, Unsgard G, Sonnewald U (1999) Decreased glutamate metabolism in cultured astrocytes in the presence of thiopental. Biochem Pharmacol 58:1075-1080.
140. Queiroz G, Gebicke-Haerter P, Schobert A, Starke K, von Kügelgen I (1997) Release of ATP from cultured rat astrocytes elicited by glutamate receptor activation. Neuroscience 78:1203-1208.
141. Ralevic V, Burnstock G (1998) Receptors for purines and pyrimidines. Pharmacol Rev 50:413-492.
142. Robinson M (2002) Regulated trafficking of neurotransmitter transporters: common notes but different melodies. J Neurochem 80:1-11.
143. Rothstein J, Martin L, Levey A, Dykes-Hoberg M, Jin L, Wu D, Nash N, Kuncl R (1994) Localization of neuronal and glial glutamate transporters. Neuron 13:713-725.
144. Rothstein J, Dykes-Hoberg M, Pardo C, Bristol L, Jin L, Kuncl R, Kanai Y, Hediger M, Wang Y, Schielke J, Welty D (1996) Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate. Neuron 16:675-686.
145. Sarup A, Larsson OM, Schousboe A (2003) GABA transporters and GABAtransaminase as drug targets. Curr Drug Targ CNS Neurol Dis 2:269-277.
146. Scheiber IF, Dringen R (2011) Copper accelerates glycolytic flux in cultured astrocytes. Neurochem Res 36: 894-903.
147. Schmidt MM, Rohwedder A, Dringen R (2011) Effects of chlorinated acetates on the glutathione metabolism and on glycolysis of cultured astrocytes. Neurotox Res 19:628-637.
148. Schousboe A, Hertz L, Svenneby G, Kvamme E (1979) Phosphate activated glutaminase activity and glutamine uptake in primary cultures of astrocytes. J Neurochem 32:943-950.
149. Schousboe A, Sonnewald U, Waagepetersen HS (2003) Differential roles of alanine in GABAergic and glutamatergic neurons. Neurochem Int 43:311-315.
150. Schousboe A, Madsen KK, White HS (2010) GABA transport inhibitors and seizure protection: the past and future. Future Med Chem 3:183-187.
151. Schousboe A, Sickmann HM, Bak LK, Schousboe I, Jajo FS, Faek SAA, Waagepetersen HS (2011) Neuron-glia interactions in glutamatergic neurotransmission: roles of oxidative and glycolytic adenosine triphosphate as energy source. J Neurosci Res 89:1926-1934.
152. Schousboe A, Westergaard N, Sonnewald U, Petersen SB, Huang R, Peng L, Hertz L (1993) Glutamate and glutamine metabolism and compartmentation in astrocytes. Dev Neurosci 15:359-366.
153. Shulman R, Hyder F, Rothman D (2001) Cerebral energetics and the glycogen shunt: neurochemical basis of functional imaging. Proc Natl Acad Sci USA 98:6417-6422.
154. Sickmann H, Schousboe A, Fosgerau K, Waagepetersen H (2005) Compartmentation of lactate originating from glycogen and glucose in cultured astrocytes. Neurochem Res 30:1295-1304.
155. Silver I, Erecin ́ska M (1994) 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 14:5068-5076.
156. Sonnewald U, Westergaard N, Hassel B, Muller TB, Unsgard G, Fonnum F, Hertz L, Schousboe A, Petersen SB (1993) NMR spectroscopic studies of 13C acetate and 13C glucose metabolism in neocortical astrocytes: evidence for mitochondrial heterogeneity. Dev Neurosci 15:351-358.
157. 5]glutamine in cultured astrocytes studied by NMR spectroscopy: First evidence of astrocytic pyruvate recycling. J Neurochem 67:2566-2572.
158. Sonnewald U, Westergaard N, Schousboe A (1997) Glutamate transport and metabolism in astrocytes. Glia 21:99-105.
159. Stenovec M, Kreft M, Grilc S, Pangrsic T, Zorec R (2008) EAAT2 density at the astrocyte plasma membrane and Ca(2+)-regulated exocytosis. Mol Membr Biol 25:203-215.
160. Subbarao K, Hertz L (1990a) Effect of adrenergic agonists on glycogenolysis in primary cultures of astrocytes. Brain Res 536:220-226.
161. Subbarao K, Hertz L (1990b) Noradrenaline induced stimulation of oxidative metabolism in astrocytes but not in neurons in primary cultures. Brain Res 527:346-349.
162. Subbarao K, Hertz L (1991) Stimulation of energy metabolism by alphaadrenergic agonists in primary cultures of astrocytes. J Neurosci Res 28:399-405.
163. 2+ influx and phospholipase D activities of a rat brain-derived type-2 astrocyte cell line, RBA-2, are mediated through P2X7 receptors. J Neurochem 73:334-343.
164. Swanson R (1992) Physiologic coupling of glial glycogen metabolism to neuronal activity in brain. Can J Physiol Pharmacol 70 Suppl: S138-144.
165. Swanson R, Choi D (1993) Glial glycogen stores affect neuronal survival during glucose deprivation in vitro. J Cereb Blood Flow Metab 13:162-169.
166. Swanson R, Yu A, Chan P, Sharp F (1990) Glutamate increases glycogen content and reduces glucose utilization in primary astrocyte culture. J Neurochem 54:490-496.
167. Sánchez-Alvarez R, Tabernero A, Medina J (2004) Endothelin-1 stimulates the translocation and upregulation of both glucose transporter and hexokinase in astrocytes: relationship with gap junctional communication. J Neurochem 89:703-714.
168. Takanaga H, Chaudhuri B, Frommer W (2008) GLUT1 and GLUT9 as major contributors to glucose influx in HepG2 cells identified by a high sensitivity intramolecular FRET glucose sensor. Biochim Biophys Acta 1778:1091-1099.
169. Tsacopoulos M, Magistretti P (1996) Metabolic coupling between glia and neurons. J Neurosci 16:877-885.
170. Van den Berg CJ, Garfinkel D (1971) A simulation study of brain compartments: metabolism of glutamate and related substances in mouse brain. Biochem J 23:211-218.
171. Vendelin M, Birkedal R (2008) Anisotropic diffusion of fluorescently labeled ATP in rat cardiomyocytes determined by raster image correlation spectroscopy. Am J Physiol Cell Physiol 295:C1302-C1315.
172. Verderio C, Matteoli M (2001) ATP mediates calcium signaling between astrocytes and microglial cells: modulation by IFN-gamma. J Immunol 166:6383-6391.
173. Vesce S, Bezzi P, Volterra A (1999) The active role of astrocytes in synaptic transmission. Cell Mol Life Sci 56:991-1000.
174. Villa-Moruzzi E, Locci-Cubeddu T, Bergamini E (1979) Effects of adrenaline administration on the activity of glycogen metabolizing enzymes in different muscle types. Pflugers Arch 379:301-302.
175. Waagepetersen HS, Hansen GH, Fenger K, Lindsay JG, Gibson G, Schousboe A (2006) Cellular mitochondrial heterogeneity in cultured astrocytes as demonstrated by immunogold labeling of alpha-ketoglutarate dehydrogenase.Glia 53:225-231.
176. Waagepetersen HS, Schousboe A (2007) Glial GABA and glutamate metabolism. In: New Enclyclopedia in Neuroscience (Squire L, Albright T, Bloom F, Gage F, Spitzer N, eds), Elsevier Ltd, Oxford, UK.
177. Waagepetersen HS, Sonnewald U, Schousboe A (2009) Energy and amino acid neurotransmitter metabolism in astrocytes. In: Astrocytes in (patho)- physiology of the nervous system (Parpura V and Haydon PG, eds), pp 177-199, Springer, Berlin, Germany.
178. Waagepetersen HS, Sonnewald U, Larsson OM, Schousboe A (2000) A possible role of alanine for ammonia transfer between astrocytes and glutamatergic neurons. J Neurochem 75:471-479.
179. Waagepetersen HS, Sonnewald U, Larsson OM, Schousboe A (2001) Multiple compartments with different metabolic characteristics are involved in biosynthesis of intracellular and released glutamine and citrate in astrocytes.Glia 35:246-252.
180. Waagepetersen HS, Qu H, Hertz L, Sonnewald U, Schousboe A (2002) Demonstration of pyruvate recycling in primary cultures of neocortical astrocytes but not in neurons. Neurochem Res 27:1431-1437.
181. Walls A, Heimbürger C, Bouman S, Schousboe A, Waagepetersen H (2009) Robust glycogen shunt activity in astrocytes: Effects of glutamatergic and adrenergic agents. Neuroscience 158:284-292.
182. Wang Z, Haydon P, Yeung E (2000) Direct observation of calcium-independent intercellular ATP signaling in astrocytes. Anal Chem 72:2001-2007.
183. Wender R, Brown A, Fern R, Swanson R, Farrell K, Ransom B (2000) Astrocytic glycogen influences axon function and survival during glucose deprivation in central white matter. J Neurosci 20:6804-6810.
184. Westergaard N, Sonnewald U, Schousboe A (1995) Metabolic trafficking between neurons and astrocytes: the glutamate/glutamine cycle revisited. Dev Neurosci 17:203-211.
185. 13 C]glutamate. Glia 17:160-168.
186. Wiesinger H, Hamprecht B, Dringen R (1997) Metabolic pathways for glucose in astrocytes. Glia 21:22-34.
187. Yu A, Drejer J, Hertz L, Schousboe A (1983) Pyruvate carboxylase activity in primary cultures of astrocytes and neurons. J Neurochem 41:1484-1487.
188. 14C-labeled glutamate in astrocytes in primary cultures. J Neurochem 39:954-960.
189. Yu ACH, Hertz L (1983) Metabolic sources of energy in astrocytes. Neurol Neurobiol 7:431-438.
190. Yu N, Martin J, Stella N, Magistretti P (1993) Arachidonic acid stimulates glucose uptake in cerebral cortical astrocytes. Proc Natl Acad Sci USA 90:4042-4046.
191. Zhang J, Wang H, Ye C, Ge W, Chen Y, Jiang Z, Wu C, Poo M, Duan S (2003) ATP released by astrocytes mediates glutamatergic activity-dependent heterosynaptic suppression. Neuron 40:971-982.
192. Zielke HR, Zielke CL, Baab PJ, Tildon JT (2007) Effect of fluorocitrate on cerebral oxidation of lactate and glucose in freely moving rats. J Neurochem 101:9-16.
193. 14C]glutamine oxidative metabolism in the rat hippocampus as determined by microdialysis. J Neurochem 71:1315-1320.
194. 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.