Astroglial glutamate transporters coordinate excitatory signaling and brain energetics

Neurochemistry International

Volumn 98, Issue , 2016, Pages 56-71

  Robinson, Michael B ^a,b   Jackson, Joshua G ^a,b  

^a CHILDREN S HOSPITAL OF PHILADELPHIA   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

EAAT; GLAST; GLT 1; Glutamate transport; Glycogen; Glycolysis; Mitochondria

Indexed keywords

ADENOSINE TRIPHOSPHATASE (POTASSIUM SODIUM); EXCITATORY AMINO ACID TRANSPORTER; EXCITATORY AMINO ACID TRANSPORTER 1; GLUTAMATE TRANSPORTER; GLUTAMIC ACID; GLYCOGEN PHOSPHORYLASE; SODIUM CALCIUM EXCHANGE PROTEIN; VESICULAR GLUTAMATE TRANSPORTER;

AMINO ACID METABOLISM; BRAIN ENERGETICS; ENERGY TRANSFER; GLYCOLYSIS; HUMAN; IMMUNOPRECIPITATION; MACROGLIA; MITOCHONDRION; NERVE CELL EXCITABILITY; NEUROVASCULAR COUPLING; NONHUMAN; PRIORITY JOURNAL; PROTEIN PROTEIN INTERACTION; PROTEIN TRANSPORT; REVIEW; SIGNAL TRANSDUCTION; ANIMAL; ASTROCYTE; BRAIN CHEMISTRY; ENERGY METABOLISM; GENETICS; GLIA; METABOLISM; PHYSIOLOGY;

ANIMALS; ASTROCYTES; BRAIN CHEMISTRY; ENERGY METABOLISM; HUMANS; NEUROGLIA; SIGNAL TRANSDUCTION; VESICULAR GLUTAMATE TRANSPORT PROTEINS;

EID: 84962406639     PISSN: 01970186     EISSN: 18729754     Source Type: Journal    
DOI: 10.1016/j.neuint.2016.03.014     Document Type: Review

References (298)

1. Abe, K., Saito, H., Involvement of Na+-K+ pump in L-glutamate clearance by cultured rat cortical astrocytes. Biol. Pharm. Bull. 23 (2000), 1051–1054.
2. Anderson, C.M., Swanson, R.A., Astrocyte glutamate transport: review of properties, regulation, and physiological functions. Glia 32 (2000), 1–14.
3. Antonicek, H., Schachner, M., The adhesion molecule on glia (AMOG) incorporated into lipid vesicles binds to subpopulations of neurons. J. Neurosci. 8 (1988), 2961–2966.
4. Aoki, C., Milner, T.A., Berger, S.B., Sheu, K.F., Blass, J.P., Pickel, V.M., Glial glutamate dehydrogenase: ultrastructural localization and regional distribution in relation to the mitochondrial enzyme, cytochrome oxidase. J. Neurosci. Res. 18 (1987), 305–318.
5. Aoyama, K., Suh, S.W., Hamby, A.M., Liu, J., Chan, W.Y., Chen, Y., Swanson, R.A., Neuronal glutathione deficiency and age-dependent neurodegeneration in the EAAC1 deficient mouse. Nat. Neurosci. 9 (2006), 119–126.
6. Arriza, J.L., Fairman, W.A., Wadiche, J.I., Murdoch, G.H., Kavanaugh, M.P., Amara, S.G., Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex. J. Neurosci. 14 (1994), 5559–5569.
7. Attwell, D., Buchan, A.M., Charpak, S., Lauritzen, M., Macvicar, B.A., Newman, E.A., Glial and neuronal control of brain blood flow. Nature 468 (2010), 232–243.
8. Azarias, G., Perreten, H., Lengacher, S., Poburko, D., Demaurex, N., Magistretti, P.J., Chatton, J.Y., Glutamate transport decreases mitochondrial pH and modulates oxidative metabolism in astrocytes. J. Neurosci. 31 (2011), 3550–3559.
9. Balcar, V.J., Johnston, G.A.R., The structural specificity of the high affinity uptake of L-glutamate and L-aspartate by rat brain slices. J. Neurochem. 19 (1972), 2657–2666.
10. Bassan, M., Liu, H., Madsen, K.L., Armsen, W., Zhou, J., Desilva, T., Chen, W., Paradise, A., Brasch, M.A., Staudinger, J., Gether, U., Irwin, N., Rosenberg, P.A., Interaction between the glutamate transporter GLT1b and the synaptic PDZ domain protein PICK1. Eur. J. Neurosci. 27 (2008), 66–82.
11. Bauer, D.E., Jackson, J.G., Genda, E.N., Montoya, M.M., Yudkoff, M., Robinson, M.B., The glutamate transporter, GLAST, participates in a macromolecular complex that supports glutamate metabolism. Neurochem. Int. 61 (2012), 566–574.
12. Beart, P.M., O'Shea, R.D., Transporters for L-glutamate: an update on their molecular pharmacology and pathological involvement. Br. J. Pharmacol. 150 (2007), 5–17.
13. Belanger, M., Allaman, I., Magistretti, P.J., Brain energy metabolism: focus on astrocyte-neuron metabolic cooperation. Cell Metab. 14 (2011), 724–738.
14. Benediktsson, A.M., Schachtele, S.J., Green, S.H., Dailey, M.E., Ballistic labeling and dynamic imaging of astrocytes in organotypic hippocampal slice cultures. J. Neurosci. Methods 141 (2005), 41–53.
15. Benediktsson, A.M., Marrs, G.S., Tu, J.C., Worley, P.F., Rothstein, J.D., Bergles, D.E., Dailey, M.E., Neuronal activity regulates glutamate transporter dynamics in developing astrocytes. Glia 60 (2012), 175–188.
16. Benjamin Kacerovsky, J., Murai, K.K., Stargazing: monitoring subcellular dynamics of brain astrocytes. Neuroscience, 2015, 10.1016/j.neuroscience.2015.07.007.
17. Bergles, D.E., Jahr, C.E., Synaptic activation of glutamate transporters in hippocampal astrocytes. Neuron 19 (1997), 1297–1308.
18. Bernardinelli, Y., Azarias, G., Chatton, J.Y., In situ fluorescence imaging of glutamate-evoked mitochondrial Na+ responses in astrocytes. Glia 54 (2006), 460–470.
19. Beutner, G., Ruck, A., Riede, B., Brdiczka, D., Complexes between porin, hexokinase, mitochondrial creatine kinase and adenylate translocator display properties of the permeability transition pore. Implication for regulation of permeability transition by the kinases. Biochim. Biophys. Acta 1368 (1998), 7–18.
20. Bianchi, M.G., Gatti, R., Torielli, L., Padoani, G., Gazzola, G.C., Bussolati, O., The glutamate transporter excitatory amino acid carrier 1 associates with the actin-binding protein alpha-adducin. Neuroscience 169 (2010), 584–595.
21. Birsa, N., Norkett, R., Higgs, N., Lopez-Domenech, G., Kittler, J.T., Mitochondrial trafficking in neurons and the role of the Miro family of GTPase proteins. Biochem. Soc. Trans. 41 (2013), 1525–1531.
22. Bittner, C.X., Valdebenito, R., Ruminot, I., Loaiza, A., Larenas, V., Sotelo-Hitschfeld, T., Moldenhauer, H., San Martin, A., Gutierrez, R., Zambrano, M., Barros, L.F., Fast and reversible stimulation of astrocytic glycolysis by k+ and a delayed and persistent effect of glutamate. J. Neurosci. 31 (2011), 4709–4713.
23. Blaustein, M.P., Lederer, W.J., Sodium/calcium exchange: its physiological implications. Physiol. Rev. 79 (1999), 763–854.
24. Boury-Jamot, B., Carrard, A., Martin, J.L., Halfon, O., Magistretti, P.J., Boutrel, B., Disrupting astrocyte-neuron lactate transfer persistently reduces conditioned responses to cocaine. Mol. Psychiatry, 2015.
25. Brown, A.M., Ransom, B.R., Astrocyte glycogen as an emergency fuel under conditions of glucose deprivation or intense neural activity. Metab. Brain Dis. 30 (2015), 233–239.
26. Buck, C.R., Jurynec, M.J., Gupta, D.K., Law, A.K., Bilger, J., Wallace, D.C., McKeon, R.J., Increased adenine nucleotide translocator 1 in reactive astrocytes facilitates glutamate transport. Exp. Neurol. 181 (2003), 149–158.
27. Calvetti, D., Somersalo, E., Menage a trois: the role of neurotransmitters in the energy metabolism of astrocytes, glutamatergic, and GABAergic neurons. J. Cereb. Blood Flow. Metab. 32 (2012), 1472–1483.
28. Campanella, M.E., Chu, H., Low, P.S., Assembly and regulation of a glycolytic enzyme complex on the human erythrocyte membrane. Proc. Natl. Acad. Sci. U. S. A. 102 (2005), 2402–2407.
29. Casale, C.H., Previtali, G., Barra, H.S., Involvement of acetylated tubulin in the regulation of Na+,K+ -ATPase activity in cultured astrocytes. FEBS Lett. 534 (2003), 115–118.
30. Casale, C.H., Previtali, G., Serafino, J.J., Arce, C.A., Barra, H.S., Regulation of acetylated tubulin/Na+,K+-ATPase interaction by L-glutamate in non-neural cells: involvement of microtubules. Biochim. Biophys. Acta 1721 (2005), 185–192.
31. Chang, D.T., Reynolds, I.J., Mitochondrial trafficking and morphology in healthy and injured neurons. Prog. Neurobiol. 80 (2006), 241–268.
32. Chaudhry, F.A., Lehre, K.P., Campagne, M.V.L., Ottersen, O.P., Danbolt, N.C., Storm-Mathisen, J., Glutamate transporters in glial plasma membranes: highly differentiated localizations revealed by quantitative ultrastructural immunocytochemistry. Neuron 15 (1995), 711–720.
33. Chaudhry, F.A., Reimer, R.J., Edwards, R.H., The glutamine commute: take the N line and transfer to the A. J. Cell Biol. 157 (2002), 349–355.
34. Chen, W., Aoki, C., Mahadomrongkul, V., Gruber, C.E., Wang, G.J., Blitzblau, R., Irwin, N., Rosenberg, P.A., Expression of a variant form of the glutamate transporter GLT1 in neuronal cultures and in neurons and astrocytes in the rat brain. J. Neurosci. 22 (2002), 2142–2152.
35. Chen, W., Mahadomrongkul, V., Berger, U.V., Bassan, M., DeSilva, T., Tanaka, K., Irwin, N., Aoki, C., Rosenberg, P.A., The glutamate transporter GLT1a is expressed in excitatory terminals of mature hippocampal neurons. J. Neurosci. 24 (2004), 1136–1148.
36. Cheng, D., Hoogenraad, C.C., Rush, J., Ramm, E., Schlager, M.A., Duong, D.M., Xu, P., Wijayawardana, S.R., Hanfelt, J., Nakagawa, T., Sheng, M., Peng, J., Relative and absolute quantification of postsynaptic density proteome isolated from rat forebrain and cerebellum. Mol. Cell Proteom. 5 (2006), 1158–1170.
37. Choi, D.W., Excitotoxic cell death. J. Neurobiol. 23 (1992), 1261–1276.
38. Cholet, N., Pellerin, L., Magistretti, P.J., Hamel, E., Similar perisynaptic glial localization for the Na+,K+-ATPase a2 subunit and the glutamate transporters GLAST and GLT-1 in the rat somatosensory cortex. Cereb. Cortex 12 (2002), 515–525.
39. Chouhan, A.K., Zhang, J., Zinsmaier, K.E., Macleod, G.T., Presynaptic mitochondria in functionally different motor neurons exhibit similar affinities for Ca2+ but exert little influence as Ca2+ buffers at nerve firing rates in situ. J. Neurosci. 30 (2010), 1869–1881.
40. Chu, H., Puchulu-Campanella, E., Galan, J.A., Tao, W.A., Low, P.S., Hoffman, J.F., Identification of cytoskeletal elements enclosing the ATP pools that fuel human red blood cell membrane cation pumps. Proc. Natl. Acad. Sci. U. S. A. 109 (2012), 12794–12799.
41. Conti, F., DiBiasi, S., Minelli, A., Rothstein, J.D., Melone, M., EAAC1, a high-affinity glutamate transporter, is localized to astrocytes and gabaergic neurons besides pyramidal cells in the rat cerebral cortex. Cereb. Cortex 8 (1998), 108–116.
42. Conti, F., Weinberg, R.J., Shaping excitation at glutamatergic synapses. Trends Neurosci. 22 (1999), 451–458.
43. Coyle, J.T., Puttfarcken, P., Oxidative stress, glutamate, and neurodegenerative disorders. Science 262 (1993), 689–695.
44. Crompton, M., Virji, S., Ward, J.M., Cyclophilin-D binds strongly to complexes of the voltage-dependent anion channel and the adenine nucleotide translocase to form the permeability transition pore. Eur. J. Biochem. 258 (1998), 729–735.
45. Crompton, M., Virji, S., Ward, J.M., Cyclophilin-D binding proteins. Biochem. Soc. Trans., 26, 1998, S330.
46. Danbolt, N.C., Pines, G., Kanner, B.I., Purification and reconstitution of the sodium- and potassium-coupled glutamate transport glycoprotein from rat brain. Biochemistry 29 (1990), 6734–6740.
47. +] coupled L-glutamate transporter purified from rat brain is located in glial cell processes. Neuroscience 51 (1992), 295–310.
48. Danbolt, N.C., Glutamate uptake. Prog. Neurobiol. 65 (2001), 1–105.
49. Debernardi, R., Magistretti, P.J., Pellerin, L., Trans-inhibition of glutamate transport prevents excitatory amino acid-induced glycolysis in astrocytes. Brain Res. 850 (1999), 39–46.
50. Dehnes, Y., Chaudhry, F.A., Ullensvang, K., Lehre, K.P., Storm-Mathisen, J., Danbolt, N.C., The glutamate transporter EAAT4 in rat cerebellar Purkinje cells: a glutamate-gated chloride channel concentrated near the synapse in the parts of the dendritic membrane facing astroglia. J. Neurosci. 18 (1998), 3606–3610.
51. Demaurex, N., Poburko, D., Frieden, M., Regulation of plasma membrane calcium fluxes by mitochondria. Biochim. Biophys. Acta 1787 (2009), 1383–1394.
52. Denton, R.M., Randle, P.J., Martin, B.R., Stimulation by calcium ions of pyruvate dehydrogenase phosphate phosphatase. Biochem. J. 128 (1972), 161–163.
53. Denton, R.M., Regulation of mitochondrial dehydrogenases by calcium ions. Biochim. Biophys. Acta 1787 (2009), 1309–1316.
54. Derouiche, A., Haseleu, J., Korf, H.W., Fine astrocyte processes contain very small mitochondria: glial oxidative capability may fuel transmitter metabolism. Neurochem. Res. 40 (2015), 2402–2413.
55. Devarajan, P., Scaramuzzino, D.A., Morrow, J.S., Ankyrin binds to two distinct cytoplasmic domains of Na,K-ATPase alpha subunit. Proc. Natl. Acad. Sci. U. S. A. 91 (1994), 2965–2969.
56. Dienel, G.A., Brain lactate metabolism: the discoveries and the controversies. J. Cereb. Blood Flow. Metab. 32 (2012), 1107–1138.
57. Dienel, G.A., Astrocytic energetics during excitatory neurotransmission: what are contributions of glutamate oxidation and glycolysis?. Neurochem. Int. 63 (2013), 244–258.
58. Dienel, G.A., Cruz, N.F., Contributions of glycogen to astrocytic energetics during brain activation. Metab. Brain Dis. 30 (2015), 281–298.
59. DiNuzzo, M., Mangia, S., Maraviglia, B., Giove, F., Regulatory mechanisms for glycogenolysis and K+ uptake in brain astrocytes. Neurochem. Int. 63 (2013), 458–464.
60. Domercq, M., Etxebarria, E., Perez-Samartin, A., Matute, C., Excitotoxic oligodendrocyte death and axonal damage induced by glutamate transporter inhibition. Glia 52 (2005), 36–46.
61. Dostanic, I., Schultz Jel, J., Lorenz, J.N., Lingrel, J.B., The alpha 1 isoform of Na,K-ATPase regulates cardiac contractility and functionally interacts and co-localizes with the Na/Ca exchanger in heart. J. Biol. Chem. 279 (2004), 54053–54061.
62. Dunlop, J., Glutamate-based therapeutic approaches: targeting the glutamate transport system. Curr. Opin. Pharmacol. 6 (2006), 103–107.
63. Eriksson, G., Peterson, A., Iverfeldt, K., Walum, E., Sodium-dependent glutamate uptake as an activator of oxidative metabolism in primary astrocyte cultures from newborn rat. Glia 15 (1995), 152–156.
64. Faden, A.I., Demediuk, P., Panter, S.S., Vink, R., The role of excitatatory amino acids and NMDA receptors in traumatic brain injury. Science 244 (1989), 798–800.
65. Feng, W., Zhang, M., Organization and dynamics of PDZ-domain-related supramodules in the postsynaptic density. Nat. Rev. Neurosci. 10 (2009), 87–99.
66. Ferkany, J., Coyle, J.T., Heterogeneity of sodium-dependent excitatory amino acid uptake mechanisms in rat brain. J. Neurosci. Res. 16 (1986), 491–503.
67. Fernandez, B., Suarez, I., Gianonatti, C., Fine structure of astrocytic mitochondria in the hypothalamus of the hamster. J. Anat. 137:Pt. 3 (1983), 483–488.
68. Figley, C.R., Stroman, P.W., The role(s) of astrocytes and astrocyte activity in neurometabolism, neurovascular coupling, and the production of functional neuroimaging signals. Eur. J. Neurosci. 33 (2011), 577–588.
69. Filosa, J.A., Morrison, H.W., Iddings, J.A., Du, W., Kim, K.J., Beyond neurovascular coupling, role of astrocytes in the regulation of vascular tone. Neuroscience, 2015, 10.1016/j.neuroscience.2015.03.064.
70. Fournier, K.M., González, M.I., Robinson, M.B., 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 (2004), 34505–34513.
71. Furness, D.N., Dehnes, Y., Akhtar, A.Q., Rossi, D.J., Hamann, M., Grutle, N.J., Gundersen, V., Holmseth, S., Lehre, K.P., Ullensvang, K., Wojewodzic, M., Zhou, Y., Attwell, D., Danbolt, N.C., A quantitative assessment of glutamate uptake into hippocampal synaptic terminals and astrocytes: new insights into a neuronal role for excitatory amino acid transporter 2 (EAAT2). Neuroscience 157 (2008), 80–94.
72. Furuta, A., Martin, L.J., Lin, C.-L.G., Dykes-Hoberg, M., Rothstein, J.D., Cellular and synaptic localization of the neuronal glutamate transporters EAAT3 and EAAT4. Neuroscience 81 (1997), 1031–1042.
73. Gameiro, A., Braams, S., Rauen, T., Grewer, C., The discovery of slowness: low-capacity transport and slow anion channel gating by the glutamate transporter EAAT5. Biophys. J. 100 (2011), 2623–2632.
74. 3H]glutamate transport in glial cultures. J. Neurochem. 64 (1995), 2572–2580.
75. Gegelashvili, G., Danbolt, N.C., Schousboe, A., Neuronal soluble factors differentially regulate the expression of the GLT1 and GLAST glutamate transporters in cultured astroglia. J. Neurochem. 69 (1997), 2612–2615.
76. Gegelashvili, G., Schousboe, A., High affinity glutamate transporters: regulation of expression and activity. Mol. Pharmacol. 52 (1997), 6–15.
77. Gegelashvili, M., Rodriguez-Kern, A., Sung, L., Shimamoto, K., Gegelashvili, G., Glutamate transporter GLAST/EAAT1 directs cell surface expression of FXYD2/gamma subunit of Na, K-ATPase in human fetal astrocytes. Neurochem. Int. 50 (2007), 916–920.
78. Genda, E.N., Jackson, J.G., Sheldon, A.L., Locke, S.F., Greco, T.M., O'Donnell, J.C., Spruce, L.A., Xiao, R., Guo, W., Putt, M., Seeholzer, S., Ischiropoulos, H., Robinson, M.B., Co-compartmentalization of the astroglial glutamate transporter, GLT-1, with glycolytic enzymes and mitochondria. J. Neurosci. 31 (2011), 18275–18288.
79. Ghosh, M., Yang, Y., Rothstein, J.D., Robinson, M.B., Nuclear Factor-kB contributes to neuron-dependent induction of GLT-1 expression in astrocytes. J. Neurosci. 31 (2011), 9159–9169.
80. Gibbs, M.E., Anderson, D.G., Hertz, L., Inhibition of glycogenolysis in astrocytes interrupts memory consolidation in young chickens. Glia 54 (2006), 214–222.
81. Golovina, V., Song, H., James, P., Lingrel, J., Blaustein, M., Regulation of Ca2+ signaling by Na+ pump alpha-2 subunit expression. Ann. N. Y. Acad. Sci. 986 (2003), 509–513.
82. Gonzalez, M.I., Susarla, B.T., Fournier, K.M., Sheldon, A.L., Robinson, M.B., Constitutive endocytosis and recycling of the neuronal glutamate transporter, excitatory amino acid carrier 1. J. Neurochem. 103 (2007), 1917–1931.
83. González, M.I., Bannerman, P.G., Robinson, M.B., Phorbol myristate acetate-dependent interaction of protein kinase Ca and the neuronal glutamate transporter EAAC1. J. Neurosci. 23 (2003), 5589–5593.
84. González, M.I., Susarla, B.T.S., Robinson, M.B., Evidence that protein kinase Ca interacts with an regulates the glial glutamate transporter GLT-1. J. Neurochem. 94 (2005), 1180–1188.
85. Gonzalez-Gonzalez, I.M., Garcia-Tardon, N., Cubelos, B., Gimenez, C., Zafra, F., The glutamate transporter GLT1b interacts with the scaffold protein PSD-95. J. Neurochem. 105 (2008), 1834–1848.
86. Gonzalez-Gonzalez, I.M., Garcia-Tardon, N., Gimenez, C., Zafra, F., Splice variants of the glutamate transporter GLT1 form hetero-oligomers that interact with PSD-95 and NMDA receptors. J. Neurochem. 110 (2009), 264–274.
87. Gramsbergen, J.B., Leegsma-Vogt, G., Venema, K., Noraberg, J., Korf, J., Quantitative on-line monitoring of hippocampus glucose and lactate metabolism in organotypic cultures using biosensor technology. J. Neurochem. 85 (2003), 399–408.
88. Greene, J.G., Greenamyre, J.T., Bioenergetics and glutamate excitotoxicity. Prog. Neurobiol. 48 (1996), 613–634.
89. Gurden, H., Uchida, N., Mainen, Z.F., Sensory-evoked intrinsic optical signals in the olfactory bulb are coupled to glutamate release and uptake. Neuron 52 (2006), 335–345.
90. Hall, C.N., Reynell, C., Gesslein, B., Hamilton, N.B., Mishra, A., Sutherland, B.A., O'Farrell, F.M., Buchan, A.M., Lauritzen, M., Attwell, D., Capillary pericytes regulate cerebral blood flow in health and disease. Nature 508 (2014), 55–60.
91. Hamai, M., Minokoshi, Y., Shimazu, T., L-Glutamate and insulin enhance glycogen synthesis in cultured astrocytes from the rat brain through different intracellular mechanisms. J. Neurochem. 73 (1999), 400–407.
92. Harris, J.J., Jolivet, R., Attwell, D., Synaptic energy use and supply. Neuron 75 (2012), 762–777.
93. Henn, F.A., Anderson, D.J., Rustad, D.G., Glial contamination of synaptosomal fractions. Brain Res. 101 (1976), 341–344.
94. Herman, M.A., Jahr, C.E., Extracellular glutamate concentration in hippocampal slice. J. Neurosci. 27 (2007), 9736–9741.
95. Hertz, L., Functional interactions between neurons and astrocytes I. Turnover and metabolism of putative amino acid transmitters. Prog. Neurobiol. 13 (1979), 277–323.
96. Hertz, L., Swanson, R.A., Newman, G.C., Marrif, H., Juurlink, B.H., Peng, L., Can experimental conditions explain the discrepancy over glutamate stimulation of aerobic glycolysis?. Dev. Neurosci. 20 (1998), 339–347.
97. Hertz, L., Peng, L., Dienel, G.A., Energy metabolism in astrocytes: high rate of oxidative metabolism and spatiotemporal dependence on glycolysis/glycogenolysis. J. Cereb. Blood Flow. Metab. 27 (2007), 219–249.
98. Hertz, L., The glutamate-glutamine (GABA) cycle: importance of late postnatal development and potential reciprocal interactions between biosynthesis and degradation. Front. Endocrinol. Lausanne, 4, 2013, 59, 10.3389/fendo.2013.00059.
99. Hertz, L., Xu, J., Song, D., Du, T., Yan, E., Peng, L., Brain glycogenolysis, adrenoceptors, pyruvate carboxylase, Na(+),K(+)-ATPase and Marie E. Gibbs' pioneering learning studies. Front. Integr. Neurosci., 7, 2013, 20.
100. Hertz, L., Xu, J., Song, D., Du, T., Li, B., Yan, E., Peng, L., Astrocytic glycogenolysis: mechanisms and functions. Metab. Brain Dis. 30 (2015), 317–333.
101. Hillman, E.M., Coupling mechanism and significance of the BOLD signal: a status report. Annu. Rev. Neurosci. 37 (2014), 161–181.
102. Ho, V.M., Lee, J.A., Martin, K.C., The cell biology of synaptic plasticity. Science 334 (2011), 623–628.
103. Hollenbeck, P.J., Saxton, W.M., The axonal transport of mitochondria. J. Cell Sci. 118 (2005), 5411–5419.
104. Holmseth, S., Dehnes, Y., Huang, Y.H., Follin-Arbelet, V.V., Grutle, N.J., Mylonakou, M.N., Plachez, C., Zhou, Y., Furness, D.N., Bergles, D.E., Lehre, K.P., Danbolt, N.C., The density of EAAC1 (EAAT3) glutamate transporters expressed by neurons in the mammalian CNS. J. Neurosci. 32 (2012), 6000–6013.
105. Howarth, C., The contribution of astrocytes to the regulation of cerebral blood flow. Front. Neurosci., 8, 2014, 103, 10.3389/fnins.2014.00103.
106. Huageto, O., Ullensveng, K., Levy, L.M., Chaudhry, F.A., Honore, T., Neilsen, M., Lehre, K.P., Danbolt, N.C., Brain glutamate transporter proteins form homomultimers. J. Biol. Chem. 271 (1996), 27715–27722.
107. Huang, Y.H., Bergles, D.E., Glutamate transporters bring competition to the synapse. Curr. Opin. Neurobiol. 14 (2004), 346–352.
108. Hyde, J.C., Robinson, N., Electron cytochemical localization of gamma-aminobutyric acid catabolism in rat cerebellar cortex. Histochemistry 49 (1976), 51–65.
109. Iadecola, C., Nedergaard, M., Glial regulation of the cerebral microvasculature. Nat. Neurosci. 10 (2007), 1369–1376.
110. Illarionova, N.B., Brismar, H., Aperia, A., Gunnarson, E., Role of Na,K-ATPase alpha1 and alpha2 isoforms in the support of astrocyte glutamate uptake. PLoS One, 9, 2014, e98469, 10.1371/journal.pone.0098469.
111. Jabaudon, D., Scanziani, M., Gähwiler, B.H., Gerber, U., Acute decrease in net glutamate upatke during energy failure. Proc. Natl. Acad. Sci. U. S. A. 97 (2000), 5610–5615.
112. Jackson, J.G., O'Donnell, J.C., Takano, H., Coulter, D.A., Robinson, M.B., Neuronal activity and glutamate uptake decrease mitochondrial mobility in astrocytes and position mitochondria near glutamate transporters. J. Neurosci. 34 (2014), 1613–1624.
113. Jackson, J.G., O'Donnell, J.C., Krizman, E., Robinson, M.B., Displacing hexokinase from mitochondrial voltage-dependent anion channel impairs GLT-1-mediated glutamate uptake but does not disrupt interactions between GLT-1 and mitochondrial proteins. J. Neurosci. Res. 93 (2015), 999–1008.
114. Jackson, J.G., Robinson, M.B., Reciprocal regulation of mitochondrial dynamics and calcium signaling in astrocyte processes. J. Neurosci. 35 (2015), 15199–15213.
115. Jackson, M., Song, W., Liu, M.-Y., Jin, L., Dykes-Hoberg, M., Lin, C.-L.G., Bowers, W.J., Federoff, H.J., Sternwels, P.C., Rothstein, J.D., Modulation of the neuronal glutamate transporter EAAT4 by two interacting proteins. Nature 410 (2001), 89–93.
116. Jares-Erijman, E.A., Jovin, T.M., FRET imaging. Nat. Biotechnol. 21 (2003), 1387–1395.
117. Jorgensen, P.L., Hakansson, K.O., Karlish, S.J., Structure and mechanism of Na,K-ATPase: functional sites and their interactions. Annu. Rev. Physiol. 65 (2003), 817–849.
118. Juhaszova, M., Blaustein, M.P., Distinct distribution of different Na+ pump alpha subunit isoforms in plasmalemma. Physiological implications. Ann. N. Y. Acad. Sci. 834 (1997), 524–536.
119. Kam, K., Nicoll, R., Excitatory synaptic transmission persists independently of the glutamate-glutamine cycle. J. Neurosci. 27 (2007), 9192–9200.
120. Kanamori, K., Ross, B.D., Kondrat, R.W., Glial uptake of neurotransmitter glutamate from the extracellular fluid studied in vivo by microdialysis and (13)C NMR. J. Neurochem. 83 (2002), 682–695.
121. Kanner, B.I., Structure and function of sodium-coupled GABA and glutamate transporters. J. Membr. Biol. 213 (2006), 89–100.
122. Kaplan, J.H., Biochemistry of Na,K-ATPase. Annu. Rev. Biochem. 71 (2002), 511–535.
123. Karaca, M., Frigerio, F., Migrenne, S., Martin-Levilain, J., Skytt, D.M., Pajecka, K., Martin-Del-Rio, R., Gruetter, R., Tamarit-Rodriguez, J., Waagepetersen, H.S., Magnan, C., Maechler, P., GDH-dependent glutamate oxidation in the brain dictates peripheral energy substrate distribution. Cell Rep. 13 (2015), 365–375.
124. Kim, K., Lee, S.G., Kegelman, T.P., Su, Z.Z., Das, S.K., Dash, R., Dasgupta, S., Barral, P.M., Hedvat, M., Diaz, P., Reed, J.C., Stebbins, J.L., Pellecchia, M., Sarkar, D., Fisher, P.B., Role of excitatory amino acid transporter-2 (EAAT2) and glutamate in neurodegeneration: opportunities for developing novel therapeutics. J. Cell Physiol. 226 (2011), 2484–2493.
125. Kinoshita, N., Kimura, K., Matsumoto, N., Watanabe, M., Fukaya, M., Ide, C., Mammalian septin Sept2 modulates the activity of GLAST, a glutamate transporter in astrocytes. Genes Cells 9 (2004), 1–14.
126. Kirischuk, S., Kettenmann, H., Verkhratsky, A., Na+/Ca2+ exchanger modulates kainate-triggered Ca2+ signaling in Bergmann glial cells in situ. FASEB J. 11 (1997), 566–572.
127. Kleene, R., Loers, G., Langer, J., Frobert, Y., Buck, F., Schachner, M., Prion protein regulates glutamate-dependent lactate transport of astrocytes. J. Neurosci. 27 (2007), 12331–12340.
128. Koch, H.P., Brown, R.L., Larsson, H.P., The glutamate-activated anion conductance in excitatory amino acid transporters is gated independently by the individual subunits. J. Neurosci. 27 (2007), 2943–2947.
129. Koehler, R.C., Roman, R.J., Harder, D.R., Astrocytes and the regulation of cerebral blood flow. Trends Neurosci. 32 (2009), 160–169.
130. Kojima, S., Nakamura, T., Nidaira, T., Nakamura, K., Ooashi, N., Ito, E., Watase, K., Tanaka, K., Wada, K., Kudo, Y., Miyakawa, H., Optical detection of synaptically induced glutamate transport in hippocampal slices. J. Neurosci. 19 (1999), 2580–2588.
131. Kristian, T., Pivovarova, N.B., Fiskum, G., Andrews, S.B., Calcium-induced precipitate formation in brain mitochondria: composition, calcium capacity, and retention. J. Neurochem. 102 (2007), 1346–1356.
132. Kugler, P., Schmitt, A., Glutamate transporter EAAC! is expressed in neurons and glial cells in the rat nervous system. Glia 27 (1999), 129–142.
133. Kugler, P., Schleyer, V., Developmental expression of glutamate transporters and glutamate dehydrogenase in astrocytes of the postnatal rat hippocampus. Hippocampus 14 (2004), 975–985.
134. Langer, J., Rose, C.R., Synaptically induced sodium signals in hippocampal astrocytes in situ. J. Physiol. 587 (2009), 5859–5877.
135. Leary, G.P., Stone, E.F., Holley, D.C., Kavanaugh, M.P., The glutamate and chloride permeation pathways are colocalized in individual neuronal glutamate transporter subunits. J. Neurosci. 27 (2007), 2938–2942.
136. Lee, A., Rayfield, A., Hryciw, D.H., Ma, T.A., Wang, D., Pow, D., Broer, S., Yun, C., Poronnik, P., Na+-H+ exchanger regulatory factor 1 is a PDZ scaffold for the astroglial glutamate transporter GLAST. Glia 55 (2007), 119–129.
137. Lencesova, L., O'Neill, A., Resneck, W.G., Bloch, R.J., Blaustein, M.P., Plasma membrane-cytoskeleton-endoplasmic reticulum complexes in neurons and astrocytes. J. Biol. Chem. 279 (2004), 2885–2893.
138. +-dependent glutamate uptake. J. Neurosci. 18 (1998), 9620–9628.
139. Li, Z., Okamoto, K., Hayashi, Y., Sheng, M., The importance of dendritic mitochondria in the morphogenesis and plasticity of spines and synapses. Cell 119 (2004), 873–887.
140. Lin, C.-L.G., Orlov, I., Ruggiero, A.M., Dykes-Hoberg, M., Lee, A., Jackson, M., Rothstein, J.D., Modulation of the neuronal glutamate transporter EAAC1 by the interacting protein GTRAP3-18. Nature 410 (2001), 84–88.
141. Linden, M., Gellerfors, P., Nelson, B.D., Pore protein and the hexokinase-binding protein from the outer membrane of rat liver mitochondria are identical. FEBS Lett. 141 (1982), 189–192.
142. Loaiza, A., Porras, O.H., Barros, L.F., Glutamate triggers rapid glucose transport stimulation in astrocytes as evidenced by real-time confocal microscopy. J. Neurosci. 23 (2003), 7337–7342.
143. Logan, W.J., Snyder, S.H., High affinity uptake systems for glycine, glutamic and aspartic acids in synaptosomes of rat central nervous tissues. Brain Res. 42 (1972), 413–431.
144. Lovatt, D., Sonnewald, U., Waagepetersen, H.S., Schousboe, A., He, W., Lin, J.H., Han, X., Takano, T., Wang, S., Sim, F.J., Goldman, S.A., Nedergaard, M., The transcriptome and metabolic gene signature of protoplasmic astrocytes in the adult murine cortex. J. Neurosci. 27 (2007), 12255–12266.
145. MacAskill, A.F., Kittler, J.T., Control of mitochondrial transport and localization in neurons. Trends Cell Biol. 20 (2009), 102–112.
146. Macaskill, A.F., Rinholm, J.E., Twelvetrees, A.E., Arancibia-Carcamo, I.L., Muir, J., Fransson, A., Aspenstrom, P., Attwell, D., Kittler, J.T., Miro1 is a calcium sensor for glutamate receptor-dependent localization of mitochondria at synapses. Neuron 61 (2009), 541–555.
147. Magi, S., Lariccia, V., Castaldo, P., Arcangeli, S., Nasti, A.A., Giordano, A., Amoroso, S., Physical and functional interaction of NCX1 and EAAC1 transporters leading to glutamate-enhanced ATP production in brain mitochondria. PLoS One, 7, 2012, e34015, 10.1371/journal.pone.0034015.
148. Magi, S., Arcangeli, S., Castaldo, P., Nasti, A.A., Berrino, L., Piegari, E., Bernardini, R., Amoroso, S., Lariccia, V., Glutamate-induced ATP synthesis: relationship between plasma membrane Na+/Ca2+ exchanger and excitatory amino acid transporters in brain and heart cell models. Mol. Pharmacol. 84 (2013), 603–614.
149. Magistretti, P.J., Allaman, I., A cellular perspective on brain energy metabolism and functional imaging. Neuron 86 (2015), 883–901.
150. Mamczur, P., Borsuk, B., Paszko, J., Sas, Z., Mozrzymas, J., Wisniewski, J.R., Gizak, A., Rakus, D., Astrocyte-neuron crosstalk regulates the expression and subcellular localization of carbohydrate metabolism enzymes. Glia 63 (2015), 328–340.
151. Marcaggi, P., Attwell, D., Role of glial amino acid transporters in synaptic transmission and brain energetics. Glia 47 (2004), 217–225.
152. Marie, H., Billups, D., Bedford, F.K., Dumoulin, A., Goyal, R.K., Longmore, G.D., Moss, S.J., Attwell, D., The amino terminus of the glial glutamate transporter GLT-1 interacts with the LIM protein Ajuba. Mol. Cell. Neurosci. 19 (2002), 152–164.
153. Martinez-Lozada, Z., Guillem, A.M., Flores-Mendez, M., Hernandez-Kelly, L.C., Vela, C., Meza, E., Zepeda, R.C., Caba, M., Rodriguez, A., Ortega, A., GLAST/EAAT1-induced glutamine release via SNAT3 in Bergmann glial cells: evidence of a functional and physical coupling. J. Neurochem. 125 (2013), 545–554.
154. Massie, A., Vandesande, F., Arckens, L., Expression of the high-affinity glutamate transporter EAAT4 in mammalian cerebral cortex. Neuroreport 12 (2001), 393–397.
155. Massie, A., Cnops, L., Smolders, I., McCullumsmith, R., Kooijman, R., Kwak, S., Arckens, L., Michotte, Y., High-affinity Na+/K+-dependent glutamate transporter EAAT4 is expressed throughout the rat fore- and midbrain. J. Comp. Neurol. 511 (2008), 155–172.
156. Mathiisen, T.M., Lehre, K.P., Danbolt, N.C., Ottersen, O.P., The perivascular astroglial sheath provides a complete covering of the brain microvessels: an electron microscopic 3D reconstruction. Glia 58 (2010), 1094–1103.
157. Matos, M., Augusto, E., Santos-Rodrigues, A.D., Schwarzschild, M.A., Chen, J.F., Cunha, R.A., Agostinho, P., Adenosine A2A receptors modulate glutamate uptake in cultured astrocytes and gliosomes. Glia 60 (2012), 702–716.
158. Matos, M., Augusto, E., Agostinho, P., Cunha, R.A., Chen, J.F., Antagonistic interaction between adenosine A2A receptors and Na+/K+-ATPase-alpha2 controlling glutamate uptake in astrocytes. J. Neurosci. 33 (2013), 18492–18502.
159. McDonald, J.W., Johnston, M.V., Physiological and pathophysiological roles of excitatory amino acids during central nervous system development. Brain Res. Rev. 15 (1990), 41–70.
160. McGrail, K.M., Phillips, J.M., Sweadner, K.J., Immunofluorescent localization of three Na,K-ATPase isozymes in the rat central nervous system: both neurons and glia can express more than one Na,K-ATPase. J. Neurosci. 11 (1991), 381–391.
161. McKenna, M.C., Sonnewald, U., Huang, X., Stevenson, J., Zielke, H.R., Exogenous glutamate concentration regulates the metabolic fate of glutamate in astrocytes. J. Neurochem. 66 (1996), 386–393.
162. McKenna, M.C., Tildon, J.T., Stevenson, J.H., Huang, X., New insights into the compartmentation of glutamate and glutamine in cultured rat brain astrocytes. Dev. Neurosci. 18 (1996), 380–390.
163. McKenna, M.C., The glutamate-glutamine cycle is not stoichiometric: fates of glutamate in brain. J. Neurosci. Res. 85 (2007), 3347–3358.
164. McKenna, M.C., Glutamate pays its own way in astrocytes. Front. Endocrinol. Lausanne, 4, 2013, 191, 10.3389/fendo.2013.00191.
165. Melone, M., Bellesi, M., Conti, F., Synaptic localization of GLT-1a in the rat somatic sensory cortex. Glia 57 (2009), 108–117.
166. Michaeli, S., Fait, A., Lagor, K., Nunes-Nesi, A., Grillich, N., Yellin, A., Bar, D., Khan, M., Fernie, A.R., Turano, F.J., Fromm, H., A mitochondrial GABA permease connects the GABA shunt and the TCA cycle, and is essential for normal carbon metabolism. Plant J. 67 (2011), 485–498.
167. Mim, C., Balani, P., Rauen, T., Grewer, C., The glutamate transporter subtypes EAAT4 and EAATs 1-3 transport glutamate with dramatically different kinetics and voltage dependence but share a common uptake mechanism. J. Gen. Physiol. 126 (2005), 571–589.
168. Minelli, A., Castaldo, P., Gobbi, P., Salucci, S., Magi, S., Amoroso, S., Cellular and subcellular localization of Na+-Ca2+ exchanger protein isoforms, NCX1, NCX2, and NCX3 in cerebral cortex and hippocampus of adult rat. Cell Calcium 41 (2007), 221–234.
169. Moore, E.D., Etter, E.F., Philipson, K.D., Carrington, W.A., Fogarty, K.E., Lifshitz, L.M., Fay, F.S., Coupling of the Na+/Ca2+ exchanger, Na+/K+ pump and sarcoplasmic reticulum in smooth muscle. Nature 365 (1993), 657–660.
170. Motori, E., Puyal, J., Toni, N., Ghanem, A., Angeloni, C., Malaguti, M., Cantelli-Forti, G., Berninger, B., Conzelmann, K.K., Gotz, M., Winklhofer, K.F., Hrelia, S., Bergami, M., Inflammation-induced alteration of astrocyte mitochondrial dynamics requires autophagy for mitochondrial network maintenance. Cell Metab. 18 (2013), 844–859.
171. Mugnaini, E., Helical filaments in astrocytic mitochondria of the corpus striatum in the rat. J. Cell Biol. 23 (1964), 173–182.
172. Muller, M.S., Pedersen, S.E., Walls, A.B., Waagepetersen, H.S., Bak, L.K., Isoform-selective regulation of glycogen phosphorylase by energy deprivation and phosphorylation in astrocytes. Glia 63 (2015), 154–162.
173. Munoz, M.F., Puebla, M., Figueroa, X.F., Control of the neurovascular coupling by nitric oxide-dependent regulation of astrocytic Ca(2+) signaling. Front. Cell Neurosci., 9, 2015, 59, 10.3389/fncel.2015.00059.
174. Murphy-Royal, C., Dupuis, J.P., Varela, J.A., Panatier, A., Pinson, B., Baufreton, J., Groc, L., Oliet, S.H., Surface diffusion of astrocytic glutamate transporters shapes synaptic transmission. Nat. Neurosci. 18 (2015), 219–226.
175. Nagao, S., Kwak, S., Kanaza, I., EAAT4, a glutamate transporter with properties of a chloride channel, is predominantly localized in purkinje cell dendrites, and forms parasagittal compartments in rat cerebellum. Neuroscience 78 (1997), 929–933.
176. Nakagawa, T., Otsubo, Y., Yatani, Y., Shirakawa, H., Kaneko, S., Mechanisms of substrate transport-induced clustering of a glial glutamate transporter GLT-1 in astroglial-neuronal cultures. Eur. J. Neurosci. 28 (2008), 1719–1730.
177. Nakashima, R.A., Mangan, P.S., Colombini, M., Pedersen, P.L., Hexokinase receptor complex in hepatoma mitochondria: evidence from N,N'-dicyclohexylcarbodiimide-labeling studies for the involvement of the pore-forming protein VDAC. Biochemistry 25 (1986), 1015–1021.
178. Namekata, K., Harada, C., Kohyama, K., Matsumoto, Y., Harada, T., Interleukin-1 stimulates glutamate uptake in glial cells by accelerating membrane trafficking of Na+/K+-ATPase via actin depolymerization. Mol. Cell Biol. 28 (2008), 3273–3280.
179. Nguyen, K.T., Buljan, V., Else, P.L., Pow, D.V., Balcar, V.J., Cardiac glycosides ouabain and digoxin interfere with the regulation of glutamate transporter GLAST in astrocytes cultured from neonatal rat brain. Neurochem. Res. 35 (2010), 2062–2069.
180. Norenberg, M.D., Martinez-Hernandez, A., Fine structural localization of glutamine synthetase in astrocytes of rat brain. Brain Res. 161 (1979), 303–310.
181. Oberheim, N.A., Takano, T., Han, X., He, W., Lin, J.H., Wang, F., Xu, Q., Wyatt, J.D., Pilcher, W., Ojemann, J.G., Ransom, B.R., Goldman, S.A., Nedergaard, M., Uniquely hominid features of adult human astrocytes. J. Neurosci. 29 (2009), 3276–3287.
182. Ohno, N., Kidd, G.J., Mahad, D., Kiryu-Seo, S., Avishai, A., Komuro, H., Trapp, B.D., Myelination and axonal electrical activity modulate the distribution and motility of mitochondria at CNS nodes of Ranvier. J. Neurosci. 31 (2011), 7249–7258.
183. Oliet, S.H.R., Piet, R., Poulain, D.A., Control of glutamate clearance and synaptic efficacy by glial coverage of neurons. Science 292 (2001), 923–926.
184. Otis, T.S., Kavanaugh, M.P., Isolation of current components and partial reaction cycles in the glial glutamate transporter EAAT2. J. Neurosci. 20 (2000), 2749–2757.
185. Otis, T.S., Brasnjo, G., Dzubay, J.A., Pratap, M., Interactions between glutamate transporters and metabotropic glutamate receptors at excitatory synapses in the cerebellar cortex. Neurochem. Int. 45 (2004), 537–544.
186. Owe, S.G., Marcaggi, P., Attwell, D., The ionic stoichiometry of the GLAST glutamate transporter in salamander retinal glia. J. Physiol. 577 (2006), 591–599.
187. Oz, G., Berkich, D.A., Henry, P.G., Xu, Y., LaNoue, K., Hutson, S.M., Gruetter, R., Neuroglial metabolism in the awake rat brain: CO2 fixation increases with brain activity. J. Neurosci. 24 (2004), 11273–11279.
188. Pappalardo, L.W., Samad, O.A., Black, J.A., Waxman, S.G., Voltage-gated sodium channel Nav 1.5 contributes to astrogliosis in an in vitro model of glial injury via reverse Na+/Ca2+ exchange. Glia 62 (2014), 1162–1175.
189. Parnis, J., Montana, V., Delgado-Martinez, I., Matyash, V., Parpura, V., Kettenmann, H., Sekler, I., Nolte, C., Mitochondrial exchanger NCLX plays a major role in the intracellular Ca2+ signaling, gliotransmission, and proliferation of astrocytes. J. Neurosci. 33 (2013), 7206–7219.
190. Pellerin, L., Magistretti, P.J., Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc. Natl. Acad. Sci. U. S. A. 91 (1994), 10625–10629.
191. Pellerin, L., Magistretti, P.J., Glutamate uptake stimulates Na+,K+-ATPase activity in astrocytes via activation of a distinct subunit highly sensitive to ouabain. J. Neurochem. 69 (1997), 2132–2137.
192. Peng, L., Swanson, R.A., Hertz, L., Effects of L-glutamate, D-aspartate, and monensin on glycolytic and oxidative glucose metabolism in mouse astrocyte cultures: further evidence that glutamate uptake is metabolically driven by oxidative metabolism. Neurochem. Int. 38 (2001), 437–443.
193. Perreten Lambert, H., Zenger, M., Azarias, G., Chatton, J.Y., Magistretti, P.J., Lengacher, S., Control of mitochondrial pH by uncoupling protein 4 in astrocytes promotes neuronal survival. J. Biol. Chem. 289 (2014), 31014–31028.
194. Petit, J.M., Gyger, J., Burlet-Godinot, S., Fiumelli, H., Martin, J.L., Magistretti, P.J., Genes involved in the astrocyte-neuron lactate shuttle (ANLS) are specifically regulated in cortical astrocytes following sleep deprivation in mice. Sleep 36 (2013), 1445–1458.
195. Petr, G.T., Sun, Y., Frederick, N.M., Zhou, Y., Dhamne, S.C., Hameed, M.Q., Miranda, C., Bedoya, E.A., Fischer, K.D., Armsen, W., Wang, J., Danbolt, N.C., Rotenberg, A., Aoki, C.J., Rosenberg, P.A., Conditional deletion of the glutamate transporter GLT-1 reveals that astrocytic GLT-1 protects against fatal epilepsy while neuronal GLT-1 contributes significantly to glutamate uptake into synaptosomes. J. Neurosci. 35 (2015), 5187–5201.
196. Petzold, G.C., Albeanu, D.F., Sato, T.F., Murthy, V.N., Coupling of neural activity to blood flow in olfactory glomeruli is mediated by astrocytic pathways. Neuron 58 (2008), 897–910.
197. Petzold, G.C., Murthy, V.N., Role of astrocytes in neurovascular coupling. Neuron 71 (2011), 782–797.
198. Pfeiffer, B., Meyermann, R., Hamprecht, B., Immunohistochemical co-localization of glycogen phosphorylase with the astroglial markers glial fibrillary acidic protein and S-100 protein in rat brain sections. Histochemistry 97 (1992), 405–412.
199. Pfeiffer-Guglielmi, B., Fleckenstein, B., Jung, G., Hamprecht, B., Immunocytochemical localization of glycogen phosphorylase isozymes in rat nervous tissues by using isozyme-specific antibodies. J. Neurochem. 85 (2003), 73–81.
200. Pochini, L., Scalise, M., Galluccio, M., Indiveri, C., Membrane transporters for the special amino acid glutamine: structure/function relationships and relevance to human health. Front. Chem., 2, 2014, 61.
201. Porras, O.H., Ruminot, I., Loaiza, A., Barros, L.F., Na(+)-Ca(2+) cosignaling in the stimulation of the glucose transporter GLUT1 in cultured astrocytes. Glia 56 (2008), 59–68.
202. Pow, D.V., Barnett, N.L., Developmental expression of excitatory amino acid transporter 5: a photoreceptor and bipolar cell glutamate transporter in rat retina. Neurosci. Lett. 280 (2000), 21–24.
203. Raichle, M.E., Mintun, M.A., Brain work and brain imaging. Annu. Rev. Neurosci. 29 (2006), 449–476.
204. Raju, K., Doulias, P.T., Evans, P., Krizman, E.N., Jackson, J.G., Horyn, O., Daikhin, Y., Nissim, I., Yudkoff, M., Nissim, I., Sharp, K.A., Robinson, M.B., Ischiropoulos, H., Regulation of brain glutamate metabolism by nitric oxide and S-nitrosylation. Sci. Signal, 8, 2015, ra68, 10.1126/scisignal.aaa4312.
205. Regan, M.R., Huang, Y.H., Kim, Y.S., Dykes-Hoberg, M.I., Jin, L., Watkins, A.M., Bergles, D.E., Rothstein, J.D., Variations in promoter activity reveal a differential expression and physiology of glutamate transporters by glia in the developing and mature CNS. J. Neurosci. 27 (2007), 6607–6619.
206. Regenold, W.T., Pratt, M., Nekkalapu, S., Shapiro, P.S., Kristian, T., Fiskum, G., Mitochondrial detachment of hexokinase 1 in mood and psychotic disorders: implications for brain energy metabolism and neurotrophic signaling. J. Psychiatry Res. 46 (2012), 95–104.
207. Reyes, R.C., Verkhratsky, A., Parpura, V., Plasmalemmal Na+/Ca2+ exchanger modulates Ca2+-dependent exocytotic release of glutamate from rat cortical astrocytes. ASN Neuro, 4, 2012, 10.1042/AN20110059.
208. Richter, K., Hamprecht, B., Scheich, H., Ultrastructural localization of glycogen phosphorylase predominantly in astrocytes of the gerbil brain. Glia 17 (1996), 263–273.
209. Rintoul, G.L., Filiano, A.J., Brocard, J.B., Kress, G.J., Reynolds, I.J., Glutamate decreases mitochondrial size and movement in primary forebrain neurons. J. Neurosci. 23 (2003), 7881–7888.
210. Roberts, P.J., Watkins, J.C., Structural requirements for the inhibition for L-glutamate uptake by glia and nerve endings. Brain Res. 85 (1975), 120–125.
211. Roberts, R.C., Roche, J.K., McCullumsmith, R.E., Localization of excitatory amino acid transporters EAAT1 and EAAT2 in human postmortem cortex: a light and electron microscopic study. Neuroscience 277 (2014), 522–540.
212. Robinson, M.B., Coyle, J.T., Glutamate and related acidic excitatory neurotransmitters: from basic science to clinical application. Faseb J. 1 (1987), 446–455.
213. 3H]glutamate transport processes in rat brain. Brain Res. 544 (1991), 196–202.
214. Robinson, M.B., Dowd, L.A., Heterogeneity and functional properties of subtypes of sodium-dependent glutamate transporters in the mammalian central nervous system. Adv. Pharmacol. 37 (1997), 69–115.
215. Robinson, M.B., The family of sodium-dependent glutamate transporters: a focus on the GLT-1/EAAT2 subtype. Neurochem. Int. 33 (1999), 479–491.
216. Rojas, H., Colina, C., Ramos, M., Benaim, G., Jaffe, E., Caputo, C., Di Polo, R., Sodium-calcium exchanger modulates the L-glutamate Ca(i) (2+) signalling in type-1 cerebellar astrocytes. Adv. Exp. Med. Biol. 961 (2013), 267–274.
217. Rose, E.M., Koo, J.C., Antflick, J.E., Ahmed, S.M., Angers, S., Hampson, D.R., Glutamate transporter coupling to Na,K-ATPase. J. Neurosci. 29 (2009), 8143–8155.
218. Rossi, D.J., Oshima, T., Attwell, D., Glutamate release in severe brain ischaemia is mainly by reversed uptake. Nature 403 (2000), 316–321.
219. Rothman, D.L., De Feyter, H.M., de Graaf, R.A., Mason, G.F., Behar, K.L., 13C MRS studies of neuroenergetics and neurotransmitter cycling in humans. NMR Biomed. 24 (2011), 943–957.
220. Rothstein, J.D., Martin, L., Levey, A.I., Dykes-Hoberg, M., Jin, L., Wu, D., Nash, N., Kuncl, R.W., Localization of neuronal and glial glutamate transporters. Neuron 13 (1994), 713–725.
221. Ryan, R.M., Vandenberg, R.J., A channel in a transporter. Clin. Exp. Pharmacol. Physiol. 32 (2005), 1–6.
222. Sato, K., Otsu, W., Otsuka, Y., Inaba, M., Modulatory roles of NHERF1 and NHERF2 in cell surface expression of the glutamate transporter GLAST. Biochem. Biophys. Res. Commun. 430 (2013), 839–845.
223. Sattler, R., Rothstein, J.D., Regulation and dysregulation of glutamate transporters. Handb. Exp. Pharmacol., 2006, 277–303.
224. +-dependent glutamate transporters by cyclic AMP analogs and neurons. Mol. Pharmacol. 53 (1998), 355–369.
225. Schneider, N., Cordeiro, S., Machtens, J.P., Braams, S., Rauen, T., Fahlke, C., Functional properties of the retinal glutamate transporters GLT-1c and EAAT5. J. Biol. Chem. 289 (2014), 1815–1824.
226. Schousboe, A., Transport and metabolism of glutamate and GABA in neurons are glial cells. Int. Rev. Neurobiol. 22 (1981), 1–45.
227. Schousboe, A., Sickmann, H.M., Walls, A.B., Bak, L.K., Waagepetersen, H.S., Functional importance of the astrocytic glycogen-shunt and glycolysis for maintenance of an intact intra/extracellular glutamate gradient. Neurotox. Res. 18 (2010), 94–99.
228. Schousboe, A., Sickmann, H.M., Bak, L.K., Schousboe, I., Jajo, F.S., Faek, S.A., Waagepetersen, H.S., Neuron-glia interactions in glutamatergic neurotransmission: roles of oxidative and glycolytic adenosine triphosphate as energy source. J. Neurosci. Res. 89 (2011), 1926–1934.
229. Schousboe, A., Scafidi, S., Bak, L.K., Waagepetersen, H.S., McKenna, M.C., Glutamate metabolism in the brain focusing on astrocytes. Adv. Neurobiol. 11 (2014), 13–30.
230. Schousboe, I., Bro, B., Schousboe, A., Intramitochondrial localization of the 4-aminobutyrate-2-oxoglutarate transaminase from ox brain. Biochem. J. 162 (1977), 303–307.
231. Schummers, J., Yu, H., Sur, M., Tuned responses of astrocytes and their influence on hemodynamic signals in the visual cortex. Science 320 (2008), 1638–1643.
232. Schwarz, T.L., Mitochondrial trafficking in neurons. Cold Spring Harb. Perspect. Biol., 5, 2013, a011304, 10.1101/cshperspect.a011304.
233. Seal, R.P., Amara, S.G., Excitatory amino acid transporters: a family in flux. Annu. Rev. Pharmacol. Toxicol. 39 (1999), 431–456.
234. Shan, D., Mount, D., Moore, S., Haroutunian, V., Meador-Woodruff, J.H., McCullumsmith, R.E., Abnormal partitioning of hexokinase 1 suggests disruption of a glutamate transport protein complex in schizophrenia. Schizophr. Res. 154 (2014), 1–13.
235. Sheean, R.K., Lau, C.L., Shin, Y.S., O'Shea, R.D., Beart, P.M., Links between L-glutamate transporters, Na+/K+-ATPase and cytoskeleton in astrocytes: evidence following inhibition with rottlerin. Neuroscience 254 (2013), 335–346.
236. Sheldon, A.L., Robinson, M.B., The role of glutamate transporters in neurodegenerative diseases and potential opportunities for intervention. Neurochem. Int. 51 (2007), 333–355.
237. Sheng, M., Hoogenraad, C.C., The postsynaptic architecture of excitatory synapses: a more quantitative view. Annu. Rev. Biochem. 76 (2007), 823–847.
238. Sheng, Z.H., Cai, Q., Mitochondrial transport in neurons: impact on synaptic homeostasis and neurodegeneration. Nat. Rev. Neurosci. 13 (2012), 77–93.
239. Shigeri, Y., Seal, R.P., Shimamoto, K., Molecular pharmacology of glutamate transporters, EAATs and VGLUTs. Brain Res. Rev. 45 (2004), 250–265.
240. Sickmann, H.M., Walls, A.B., Schousboe, A., Bouman, S.D., Waagepetersen, H.S., Functional significance of brain glycogen in sustaining glutamatergic neurotransmission. J. Neurochem. 109:Suppl. 1 (2009), 80–86.
241. Sims, K.D., Robinson, M.B., Expression patterns and regulation of glutamate transporters in the developing and adult nervous system. Crit. Rev. Neurobiol. 13 (1999), 169–197.
242. Song, H., Lee, M.Y., Kinsey, S.P., Weber, D.J., Blaustein, M.P., An N-terminal sequence targets and tethers Na+ pump alpha2 subunits to specialized plasma membrane microdomains. J. Biol. Chem. 281 (2006), 12929–12940.
243. Sonnewald, U., Westergaard, N., Petersen, S.B., Unsgard, G., Schousboe, A., Metabolism of [U-13C]glutamate in astrocytes studied by 13C NMR spectroscopy: incorporation of more label into lactate than into glutamine demonstrates the importance of the tricarboxylic acid cycle. J. Neurochem. 61 (1993), 1179–1182.
244. Sonnewald, U., Westergaard, N., Schousboe, A., Glutamate transport and metabolism in astrocytes. Glia 21 (1997), 56–63.
245. Sonnewald, U., Glutamate synthesis has to be matched by its degradation - where do all the carbons go?. J. Neurochem. 131 (2014), 399–406.
246. Spanaki, C., Plaitakis, A., The role of glutamate dehydrogenase in mammalian ammonia metabolism. Neurotox. Res. 21 (2012), 117–127.
247. Stanley, I.A., Ribeiro, S.M., Gimenez-Cassina, A., Norberg, E., Danial, N.N., Changing appetites: the adaptive advantages of fuel choice. Trends Cell Biol. 24 (2014), 118–127.
248. Stephen, T.L., Gupta-Agarwal, S., Kittler, J.T., Mitochondrial dynamics in astrocytes. Biochem. Soc. Trans. 42 (2014), 1302–1310.
249. Stephen, T.L., Higgs, N.F., Sheehan, D.F., Al Awabdh, S., Lopez-Domenech, G., Arancibia-Carcamo, I.L., Kittler, J.T., Miro1 regulates activity-driven positioning of mitochondria within astrocytic processes apposed to synapses to regulate intracellular calcium signaling. J. Neurosci. 35 (2015), 15996–16011.
250. Stobart, J.L., Anderson, C.M., Multifunctional role of astrocytes as gatekeepers of neuronal energy supply. Front. Cell Neurosci., 7, 2013, 38.
251. Storm-Mathisen, J., Leknes, A.K., Bore, A.T., Vaaland, J.L., Edminson, P., Haug, F.M., Ottersen, O.P., First visualization of glutamate and GABA in neurones by immunocytochemistry. Nature 301 (1983), 517–520.
252. Sui, D., Wilson, J.E., Structural determinants for the intracellular localization of the isozymes of mammalian hexokinase: intracellular localization of fusion constructs incorporating structural elements from the hexokinase isozymes and the green fluorescent protein. Arch. Biochem. Biophys. 345 (1997), 111–125.
253. Sun, T., Qiao, H., Pan, P.Y., Chen, Y., Sheng, Z.H., Motile axonal mitochondria contribute to the variability of presynaptic strength. Cell Rep. 4 (2013), 413–419.
254. Sun, W., Shchepakin, D., Kalachev, L.V., Kavanaugh, M.P., Glutamate transporter control of ambient glutamate levels. Neurochem. Int. 73 (2014), 146–151.
255. Susarla, B.T.S., Robinson, M.B., Rottlerin, an inhibitor of protein kinase Cdelta (PKCδ), inhibits astrocytic glutamate transport activity and reduces GLAST immunoreactivity by a mechanism that appears to be PKCdelta-independent. J. Neurochem. 86 (2003), 635–645.
256. Sutherland, M.L., Delaney, T.A., Noebels, J.L., Glutamate transporter mRNA expression in proliferative zones of the developing and adult murine CNS. J. Neurosci. 16 (1996), 2191–2207.
257. Suzuki, A., Stern, S.A., Bozdagi, O., Huntley, G.W., Walker, R.H., Magistretti, P.J., Alberini, C.M., Astrocyte-neuron lactate transport is required for long-term memory formation. Cell. 144 (2011), 810–823.
258. Swanson, R.A., Yu, A.C., Chan, P.H., Sharp, F.R., Glutamate increases glycogen content and reduces glucose utilization in primary astrocyte culture. J. Neurochem. 54 (1990), 490–496.
259. Swanson, R.A., Astrocyte glutamate uptake during chemical hypoxia in vitro. Neurosci. Lett. 147 (1992), 143–146.
260. Swanson, R.A., Chen, J., Graham, S.H., Glucose can fuel glutamate uptake in ischemic brain. J. Cereb. Blood Flow. Metab. 14 (1994), 1–6.
261. Swanson, R.A., Benington, J.H., Astrocyte glucose metabolism under normal and pathological conditions in vitro. Dev. Neurosci. 18 (1996), 515–521.
262. Swanson, R.A., Liu, J., Miller, J.W., Rothstein, J.D., Farrell, K., Stein, B.A., Longuemare, M.C., Neuronal regulation of glutamate transporter subtype expression in astrocytes. J. Neurosci. 17 (1997), 932–940.
263. Takahashi, S., Driscoll, B.F., Law, M.J., Sokoloff, L., Role of sodium and potassium ions in regulation of glucose metabolism in cultured astroglia. Proc. Natl. Acad. Sci. U. S. A. 92 (1995), 4616–4620.
264. Tanaka, J., Ichikawa, R., Watanabe, M., Tanaka, K., Inoue, Y., Extra-junctional localization of glutamate transporter EAAT4 at excitatory Purkinje cell synapses. NeuroReport 8 (1997), 2461–2464.
265. Tanaka, K., Watase, K., Manabe, T., Yamada, K., Watanabe, M., Takahashi, K., Iwama, H., Nishikawa, T., Ichihara, N., Kikuchi, T., Okuyama, S., Kawashima, N., Hori, S., Takimoto, M., Wada, K., Epilepsy and exacerbation of brain injury in mice lacking the glutamate transporter GLT-1. Science 276 (1997), 1699–1702.
266. Tanaka, K., Functions of glutamate transporters in the brain. Neurosci. Res. 37 (2000), 15–19.
267. Tani, H., Dulla, C.G., Farzampour, Z., Taylor-Weiner, A., Huguenard, J.R., Reimer, R.J., A local glutamate-glutamine cycle sustains synaptic excitatory transmitter release. Neuron 81 (2014), 888–900.
268. Taxt, T., Storm-Mathisen, J., Uptake of D-aspartate and L-glutamate in excitatory axon terminals in hippocampus: autoradiographic and biochemical comparisons with gamma-aminobutyrate and other amino acids in normal rats and rats with lesions. Neuroscience 11 (1984), 79–100.
269. Tian, J., Cai, T., Yuan, Z., Wang, H., Liu, L., Haas, M., Maksimova, E., Huang, X.Y., Xie, Z.J., Binding of Src to Na+/K+-ATPase forms a functional signaling complex. Mol. Biol. Cell. 17 (2006), 317–326.
270. Torres, F.V., Hansen, F., Locks-Coelho, L.D., Increase of extracellular glutamate concentration increases its oxidation and diminishes glucose oxidation in isolated mouse hippocampus: reversible by TFB-TBOA. J. Neurosci. Res. 91 (2013), 1059–1065.
271. Torres-Salazar, D., Fahlke, C., Neuronal glutamate transporters vary in substrate transport rate but not in unitary anion channel conductance. J. Biol. Chem. 282 (2007), 34719–34726.
272. Tran, C.H., Gordon, G.R., Acute two-photon imaging of the neurovascular unit in the cortex of active mice. Front. Cell Neurosci., 9, 2015, 11, 10.3389/fncel.2015.00011.
273. Trotti, D., Danbolt, N.C., Volterra, A., Glutamate transporters are oxidant-vulnerable: a molecular link between oxidative and excitotoxic neurodegeneration. Trends Pharmacol. Sci. 19 (1998), 328–334.
274. Tzingounis, A.V., Wadiche, J.I., Glutamate transporters: confining runaway excitation by shaping synaptic transmission. Nat. Rev. Neurosci. 8 (2007), 935–947.
275. Ugbode, C.I., Hirst, W.D., Rattray, M., Neuronal influences are necessary to produce mitochondrial co-localization with glutamate transporters in astrocytes. J. Neurochem. 130 (2014), 668–677.
276. Vandenberg, R.J., Ryan, R.M., Mechanisms of glutamate transport. Physiol. Rev. 93 (2013), 1621–1657.
277. Voutsinos-Porche, B., Bonvento, G., Tanaka, K., Steiner, P., Welker, E., Chatton, J.Y., Magistretti, P.J., Pellerin, L., Glial glutamate transporters mediate a functional metabolic crosstalk between neurons and astrocytes in the mouse developing cortex. Neuron 37 (2003), 275–286.
278. Waagepetersen, H.S., Hansen, G.H., Fenger, K., Lindsay, J.G., Gibson, G., Schousboe, A., Cellular mitochondrial heterogeneity in cultured astrocytes as demonstrated by immunogold labeling of alpha-ketoglutarate dehydrogenase. Glia 53 (2006), 225–231.
279. Wadiche, J.I., Amara, S.G., Kavanaugh, M.P., Ion fluxes associated with excitatory amino acid transport. Neuron 15 (1995), 721–728.
280. Watase, K., Hashimoto, K., Kano, M., Yamada, K., Watanabe, M., Inoue, Y., Okuyama, S., Sakagawa, T., Ogawa, S.-i., Kawachima, N., Hori, S., Takimoto, M., Wada, K., Tanaka, K., Motor discoordination and increased susceptibility to cerebellar injury in GLAST mutant mice. Eur. J. Neurosci. 10 (1998), 976–988.
281. Watts, A.G., Sanchez-Watts, G., Emanuel, J.R., Levenson, R., Cell-specific expression of mRNAs encoding Na+,K(+)-ATPase alpha- and beta-subunit isoforms within the rat central nervous system. Proc. Natl. Acad. Sci. U. S. A. 88 (1991), 7425–7429.
282. Weber, B., Barros, L.F., The astrocyte: powerhouse and recycling center. Cold Spring Harb. Perspect. Biol., 7, 2015.
283. Wersinger, E., Schwab, Y., Sahel, J.A., Rendon, A., Pow, D.V., Picaud, S., Roux, M.J., The glutamate transporter EAAT5 works as a presynaptic receptor in mouse rod bipolar cells. J. Physiol. 577 (2006), 221–234.
284. Whitelaw, B.S., Robinson, M.B., Inhibitors of glutamate dehydrogenase block sodium-dependent glutamate uptake in rat brain membranes. Front. Endocrinol. Lausanne, 4, 2013, 123.
285. Xie, Z., Cai, T., Na+-K+–ATPase-mediated signal transduction: from protein interaction to cellular function. Mol. Interv. 3 (2003), 157–168.
286. Xu, N.J., Bao, L., Fan, H.P., Bao, G.B., Pu, L., Lu, Y.J., Wu, C.F., Zhang, X., Pei, G., Morphine withdrawal increases glutamate uptake and surface expression of glutamate transporter GLT1 at hippocampal synapses. J. Neurosci. 23 (2003), 4775–4784.
287. Yang, J., Ruchti, E., Petit, J.M., Jourdain, P., Grenningloh, G., Allaman, I., Magistretti, P.J., Lactate promotes plasticity gene expression by potentiating NMDA signaling in neurons. Proc. Natl. Acad. Sci. U. S. A. 111 (2014), 12228–12233.
288. Yi, J.H., Hazell, A.S., Excitotoxic mechanisms and the role of astrocytic glutamate transporters in traumatic brain injury. Neurochem. Int. 48 (2006), 394–403.
289. Yu, A.C., Schousboe, A., Hertz, L., Metabolic fate of 14C-labeled glutamate in astrocytes in primary cultures. J. Neurochem. 39 (1982), 954–960.
290. Yu, Y.X., Shen, L., Xia, P., Tang, Y.W., Bao, L., Pei, G., Syntaxin 1A promotes the endocytic sorting of EAAC1 leading to inhibition of glutamate transport. J. Cell Sci. 119 (2006), 3776–3787.
291. Yuan, Z., Cai, T., Tian, J., Ivanov, A.V., Giovannucci, D.R., Xie, Z., Na/K-ATPase tethers phospholipase C and IP3 receptor into a calcium-regulatory complex. Mol. Biol. Cell. 16 (2005), 4034–4045.
292. Zahler, R., Zhang, Z.T., Manor, M., Boron, W.F., Sodium kinetics of Na,K-ATPase alpha isoforms in intact transfected HeLa cells. J. Gen. Physiol. 110 (1997), 201–213.
293. Zaid, H., Talior-Volodarsky, I., Antonescu, C., Liu, Z., Klip, A., GAPDH binds GLUT4 reciprocally to hexokinase-II and regulates glucose transport activity. Biochem. J. 419 (2009), 475–484.
294. Zerangue, N., Kavanaugh, M.P., Flux coupling in a neuronal glutamate transporter. Nature 383 (1996), 634–637.
295. Zhang, C.L., Ho, P.L., Kintner, D.B., Sun, D., Chiu, S.Y., Activity-dependent regulation of mitochondrial motility by calcium and Na/K-ATPase at nodes of Ranvier of myelinated nerves. J. Neurosci. 30 (2010), 3555–3566.
296. Zhang, Y., Chen, K., Sloan, S.A., Bennett, M.L., Scholze, A.R., O'Keeffe, S., Phatnani, H.P., Guarnieri, P., Caneda, C., Ruderisch, N., Deng, S., Liddelow, S.A., Zhang, C., Daneman, R., Maniatis, T., Barres, B.A., Wu, J.Q., An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex. J. Neurosci. 34 (2014), 11929–11947.
297. Zielke, H.R., Collins, R.M. Jr., Baab, P.J., Huang, Y., Zielke, C.L., Tildon, J.T., Compartmentation of [14C]glutamate and [14C]glutamine oxidative metabolism in the rat hippocampus as determined by microdialysis. J. Neurochem. 71 (1998), 1315–1320.
298. Zou, S., Pita-Almenar, J.D., Eskin, A., Regulation of glutamate transporter GLT-1 by MAGI-1. J. Neurochem. 117 (2011), 833–840.