CoChat
Sign Up
Cited by 76Neuroscience and Neuropharmacology ResearchAmino Acid Enzymes and MetabolismNeuroinflammation and Neurodegeneration Mechanisms

Localization of excitatory amino acid transporters EAAT1 and EAAT2 in human postmortem cortex: A light and electron microscopic study

Open access
Roberts, R.C., Roche, J.K., McCullumsmith, R.E.·2014·Neuroscience
DOI 10.1016/j.neuroscience.2014.07.019PMC PMC4164610
Open this paper in CoChat — free account

Abstract

The process of glutamate release, activity, and reuptake involves the astrocyte, the presynaptic and postsynaptic neurons. Glutamate is released into the synapse and may occupy and activate receptors on both neurons and astrocytes. Glutamate is rapidly removed from the synapse by a family of plasma membrane excitatory amino acid transporters (EAATs), also localized to neurons and astrocytes. The purpose of the present study was to examine EAAT labeling in the postmortem human cortex at the light and electron microscopic (EM) levels. The postmortem prefrontal cortex was processed for EAAT1 and EAAT2 immunohistochemistry. At the light microscopic level, EAAT1 and EAAT2 labeling was found in both gray and white matter. Most cellular labeling was in small cells which were morphologically similar to glia. In addition, EAAT1-labeled neurons were scattered throughout, some of which were pyramidal in shape. At the EM level, EAAT1 and EAAT2 labeling was found in astrocytic soma and processes surrounding capillaries. EAAT labeling was also found in small astrocytic processes adjacent to axon terminals forming asymmetric (glutamatergic) synapses. While EAAT2 labeling was most prevalent in astrocytic processes, EAAT1 labeling was also present in neuronal processes including the soma, axons, and dendritic spines. Expression of EAAT1 protein on neurons may be due to the hypoxia associated with the postmortem interval, and requires further confirmation. The localization of EAATs on the astrocytic plasma membrane and adjacent to excitatory synapses is consistent with the function of facilitating glutamate reuptake and limiting glutamate spillover. Establishment that EAAT1 and EAAT2 can be measured at the EM level in human postmortem tissues will permit testing of hypotheses related to these molecules in diseases lacking analogous animal models.

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

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

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

Integrity signals

Registry

Crossref · 10.1016/j.neuroscience.2014.07.019

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

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

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

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

Claims other papers make about this one

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

Self-check

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

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

Cites

Flagged first, then by citations

Research works printed but not linked: 122

  1. Arriza JL Furman WA Wadiche JI Murdoch GH Kavanaugh MP Amara SG Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex. J Neurosci 1994 14 5559 5569 7521911 PMC6577102
  2. Arriza JL Eliasof S Kavanaugh MP Amara SG Excitatory amino acid transporter 5, a retinal glutamate transporter coupled to a chloride conductance. Proc Natl Acad Sci USA 1997 94 4155 4160 9108121 PMC20584
  3. Baker DA Madayag A Kristiansen LV Meador-Woodruff JH Haroutunian V Raju I Contribution of cystine-glutamate antiporters to the psychotomimetic effects of phencyclidine. Neuropsychopharmacology 2008 33 7 1760 1772 17728701 PMC3907109
  4. Balazs R Machiyama Y Hammond BJ Julian T Richter D The operation of the gamma-aminobutyrate bypath of the tricarboxylicacid cycle in brain tissue in vitro. Biochem 1970 J116 445 461 PMC1185383 5435689
  5. Bar-Peled O Ben-Hur H Biegon A Groner Y Dewhurst S Furuta A Rothstein JD Distribution of glutamate transporter subtypes during human brain development. J Neurochem 1997 69 6 2571 80 9375691
  6. Bassan M Liu H Madsen KL Armsen W Zhou J Desilva T Chen W Paradise A Brasch MA Staudinger J Gether U Irwin N Rosenberg PA Interaction between the glutamate transporter GLT1b and the synaptic PDZ domain protein PICK1. Eur J Neurosci 2008 1 66 82 18184314 PMC4341970
  7. Bauer D Gupta D Harotunian V Meador-Woodruff JH McCullumsmith RE Abnormal expression of glutamate transporter and transporter interacting molecules in prefrontal cortex in elderly patients with schizophrenia. Schizophr Res 2008 104 108 20 18678470 PMC2656372
  8. Bauer D Haroutunian V Meador-Woodruff JH McCullumsmith RE Abnormal glycosylation of EAAT1 and EAAT2 in prefrontal cortex of elderly patients with schizophrenia. Schizophr Res 2010 117 1 92 98 19716271 PMC2822023
  9. Berger UV Hediger MA Comparative analysis of glutamate transporter expression in rat brain using differential double in situ hybridization. Anat Embryol (Berl) 1998 198 1 13 30 9683064
  10. Berkich DA Ola MS Cole J Sweatt AJ Hutson SM LaNoue KF Mitochondrial transport proteins of the brain. J Neurosci Res 2007 85 15 3367 77 17847082
  11. Bjørnsen LP Eid T Holmseth S Danbolt NC Spencer DD de Lanerolle NC Changes in glial glutamate transporters in human epileptogenic hippocampus: inadequate explanation for high extracellular glutamate during seizures. Neurobiol Dis 2007 25 2 319 30 17112731
  12. Bridges R Lutgen V Lobner D Baker AM Thinking outside the cleft to understand synaptic activity: Contribution of the cystine-glutamate antiporter (system xc-) to normal and pathological glutamatergic signaling. Pharmacol Rev 2012 2012 64 3 PMC3400835 22759795
  13. Brooks-Kayal AR Munir M Jin H Robinson MB The glutamate transporter, GLT-1, is expressed in cultured hippocampal neurons. Neurochem Int 1998 33 95 100 9761452
  14. Chalifoux JR Carter AG Glutamate spillover promotes the generation of NMDA spikes. J Neurosci 2011 31 16435 16446 22072693 PMC3235338
  15. Chaudhry FA Lebre KP van Lookeren Campagne M Ottersen OP Danholt NC Storm-Mathisen J Glutamate transporters in glial plasma membranes: highly differentiated localizations revealed by quantitative ultrastructural immunocytochemistry. Neuron 1995 15 711 720 7546749
  16. Chen W Aoki C Mahadomrongkul V Gruber CE Wang GJ Blitzblau R Irwin N Rosenberg PA Expression of a variant form of the glutamate transporter GLT1 in neuronal cultures and in neurons and astrocytes in the rat brain. J Neurosci 2002 22 6 2142 52 11896154 PMC2849837
  17. Chen W Mahadomrongkul V Berger UV Bassan M DeSilva T Tanaka K Irwin N Aoki C Rosenberg PA The glutamate transporter GLT1a is expressed in excitatory axon terminals of mature hippocampal neurons. J Neurosci 2004 24 1136 1148 14762132 PMC2849838
  18. Cholet N Pellerin L Magistretti PJ Hamel E Similar perisynaptic glial localization for the Na+,K+-ATPase alpha 2 subunit and the glutamate transporters GLAST and GLT-1 in the rat somatosensory cortex. Cereb Cortex 2002 12 5 515 25 11950769
  19. Conti F DeBiasi S Minelli A Rothstein JD 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 1998 8 108 116 9542890
  20. Danbolt NC Glutamate uptake. Progress in Neurobiology 2001 65 1 105 11369436
  21. Danbolt NC Chaudhry FA Dehnes Y Lehre KP Levy LM Ullensvang K Storm-Mathisen J Properties and localization of glutamate transporters. Prog Brain Res 1998 116 23 43 9932368
  22. Danbolt NC Storm-Mathisen J Kanner BI An [Na.+K.]coupled L-glutamate transporter purified from rat brain is located in glial cell processes. Neuroscience 1992 51 295 310 1465194
  23. Dehnes Y Chaudhry FA Ullensvang K Lehre KP Storm-Mathisen J Danbolt NC The glutamate transporter EAAT4 in rat cerebellar Purkinje cells: a glutamate-gated chloride channel concentrated near the synapse in parts of the dendritic membrane facing astroglia. J Neurosci 1998 18 10 3606 19 9570792 PMC6793133
  24. DeSilva TM Borenstein NS Volpe JJ Kinney HC Rosenberg PA Expression of EAAT2 in neurons and protoplasmic astrocytes during human cortical development. J Comp Neurol 2012 520 17 3912 3932 22522966 PMC3781602
  25. Desilva TM Kinney HC Borenstein NS Trachtenberg FL Irwin N Volpe JJ Rosenberg PA The glutamate transporter EAAT2 is transiently expressed in developing human cerebral white matter. J Comp Neurol 2007 501 879 890 17311320 PMC8603423
  26. Divak I Fonnum F Storm-Mathisen J High affinity uptake of glutamte in terminals of corticostriatal axons. Nature 1997 266 377 378 859607
  27. Drew GM Mitchell VA Vaughan CW Glutamate spillover modulates GABAergic synaptic transmission in the rat midbrain periaqueductal grey via metabotropic glutamate receptors and endocannabinoid signaling. J Neurosci 2008 28 808 15 18216189 PMC6670993
  28. Fairman WA Vandenberg RJ Arriza JL Kavanaugh MP Amara SG An excitatory amino-acid transporter with properties of a ligand-gated chloride channel. Nature 1995 375 599 603 7791878
  29. Fiermonte G Palmieri L Todisco S Agrimi G Palmieri F Walker JE Identification of the mitochondrial glutamate transporter. Bacterial expression, reconstitution, functional characterization, and tissue distribution of two human isoforms. J Biol Chem 2002 277 22 19289 94 11897791
  30. Furness DN Dehnes Y Akhtar AQ Rossi DJ Hamann M Grutle NJ Gundersen V Holmseth S Lehre KP Ullensvang K Wojewodzic M Zhou Y Attwell D Danbolt NC 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 2008 157 1 80 94 18805467 PMC2775085
  31. Furuta A Martin LJ Lin CLG Dykes-Hoberg M Rothstein JD Cellular and synaptic localization of the neuronal glutamate transporters excitatory amino acid transporter 3 and 4. Neuroscience 1997 81 1031 1042 9330365
  32. Gardiner RB Ullensvang K Danbolt NC Caveney S Donly BC Cellular distribution of a high-affinity glutamate transporter in the nervous system of the cabbage looper Trichoplusia ni. J Exp Biol 2002 205 2605 2613 12151366
  33. Genda EN Jackson JG Sheldon AL Locke SF Greco TM O'Donnell JC Spruce LA Xiao R Guo W Putt M Seeholzer S Ischiropoulos H Robinson MB Co-compartmentalization of the astroglial glutamate transporter, GLT-1, with glycolytic enzymes and mitochondria. J Neuroscience 2011 31 50 18275 18288 PMC3259858 22171032
  34. Ginsberg SD Martin LJ Rothstein JD Regional Deafferentiation Down-Regulates Subtypes of Glutamate Transporter Protein. J. Neurochem 1995 65 2800 03 7595581
  35. Gonzalez-Gonzalez IM Garcia-Tardon N Cubelos B Gimenez C Zafra F The glutamate transporter GLT1b interacts with the scaffold protein PSD-95. J Neurochem 2008 105 1834 1848 18248606
  36. Grosche J Kettenmann H Reichenbach A Bergmann glial cells form distinct morphological structures to interact with cerebellar neurons. J Neurosci Res 2002 68 2 138 49 11948659
  37. Grosche J Matyash V Moller T Verkhratsky A Reichenbach A Kettenmann H Microdomains for neuron-glia interaction: parallel fiber signaling to Bergmann glial cells. Nat Neurosci 1999 2 2 139 43 10195197
  38. Gundersen V Danbolt NC Ottersen OP Storm-Mathisen J Demonstration of glutamate/aspartate uptake activity in nerve endings by use of antibodies recognizing exogenous D-aspartate. Neuroscience 1993 57 97 111 7904057
  39. Gundersen V Ottersen OP Storm-Mathisen J Selective excitatory amino acid uptake in glutamatergic nerve terminals and in glia in the rat striatum: quantitative electron microscopic immunocytochemistry of exogenous (D)-aspartate and endogenous glutamate and GABA. Eur J Neurosci 1996 8 4 758 65 9081627
  40. Hardingham GE Bading H Coupling of extrasynaptic NMDA receptors to a CREB shut-off pathway is developmentally regulated. Biochim Biophys Acta 2002 1600 148 153 12445470
  41. Haugeto Ø Ullensvang K Levy LM Chaudhry FA Honoré T Nielsen M Lehre KP Danbolt NC Brain glutamate transporter proteins form homomultimers. J Biol Chem 1996 271 27715 27722 8910364
  42. Haydon PG Carmignoto G Astrocyte control of synaptic transmission and neurovascular coupling. Physiological reviews 2006 86 3 1009 31 16816144
  43. Hawkins RA O'Kane RL Simpson IA Viña JR Structure of the blood-brain barrier and its role in the transport of amino acids. J Nutr 2006 136 1 Suppl 218S 26S 16365086
  44. Hees B Danbolt NC Kanner BI Haase W Heitmann K Koepsell H A monoclonal antibody against a Na(+)-L-glutamate cotransporter from rat brain. J Biol Chem 1992 267 32 23275 23281 1429674
  45. Helms HC Madelung R Waagepetersen HS Nielsen CU Brodin B In vitro evidence for the brain glutamate efflux hypothesis: brain endothelial cells cocultured with astrocytes display a polarized brain-to-blood transport of glutamate. Glia 2012 60 6 882 93 22392649
  46. Holmseth S Dehnes Y Huang YH Follin-Arbelet VV Grutle NJ Mylonakou MN Plachez C Zhou Y Furness DN Bergles DE Lehre KP Danbolt NC The density of EAAC1 (EAAT3) glutamate transporters expressed by neurons in the mammalian CNS. J Neurosci 25 2012 32 17 6000 6013 PMC4031369 22539860
  47. Holmseth S Scott HA Real K Lehre KP Leergaard TB Bjaalie JG Danbolt NC The concentrations and distributions of three C-terminal variants of the GLT1 (EAAT2; slc1a2) glutamate transporter protein in rat brain tissue suggest differential regulation. Neuroscience 2009 162 4 1055 71 19328838
  48. Hu WH Walters WM Xia XM Karmally SA Bethea JR Neuronal glutamate transporter EAAT4 is expressed in astrocytes. Glia 2003 44 1 13 25 12951653
  49. Huerta I McCullumsmith RE Haroutunian V Giménez-Amaya JM Meador-Woodruff JH Expression of excitatory amino acid transporter interacting protein transcripts in the thalamus in schizophrenia. Synapse 2006 59 394 402 16485262
  50. Ikematsu K Tsuda R Orihara Y Nakasono I The expression of excitatory amino acid transporter 2 (EAAT2) in forensic autopsy cases. Forensic Sci Int 2001 118 49 55 11343855
  51. Inage YW Itoh M Wada K Takashima S Expression of two glutamate transporters, GLAST and EAAT4, in the human cerebellum: their correlation in development and neonatal hypoxic-ischemic damage. J Neuropathol Exp Neurol 1998 57 554 562 9630235
  52. Itoh M Watanabe Y Watanabe M Tanaka K Wada K Takashima S Expression of a glutamate transporter subtype, EAAT4, in the developing human cerebellum. Brain Res 1997 767 265 271 9367257
  53. Kanai Y Hediger MA Primary structure and functional characterization of a high affinity glutamate transporter. Nature 1992 360 467 471 1280334
  54. Karlsson RM Heilig M Holmes A Loss of Glial Glutamate and Aspartate transporter (Excitatory Amino Acid Transporter 1) Causes Locomotor Hyperactivity and Exaggerated responses to Psychotomimetics: Rescue by Haloperidol and Metabotropic Glutamate 2/3 Agonist. Biol Psychiatry 2008 64 9 810 14 18550032 PMC2696047
  55. Kullmann DM Asztely F Extrasynaptic glutamate spillover in the hippocampus: evidence and implications. Trends Neurosci 1998 21 8 14 9464678
  56. Lee A Anderson AR Stevens M Beasley S Barnett NL Pow DV Excitatory Amino Acid Transporter 5 is widely expressed in peripheral tissues. Eur J Histochem 2013 57 1 e11 23549460 PMC3683608
  57. Lehre KP Levy LM Ottersen OP Storm-Mathisen J Danbolt NC Differential expression of two glial glutamate transporters in the rat brain: quantitative and immunocytochemical observations. J Neurosci 1995 15 1835 1853 7891138 PMC6578153
  58. Leveille F El-Gaamouch F Gouix E Lecocq M Lobner D Nicole O Buisson A Neuronal viability is controlled by a functional relation between synaptic and extrasynaptic NMDA receptors. Faseb J 2008 12 4258 4271 18711223
  59. Levenson J Weeber E Selcher JC Kategaya LS Sweatt JD Eskin A Long-term potentiation and contextual fear conditioning increase neuronal glutamate uptake. Nature Neurosci 2002 5 155 161 11788834
  60. Levy LM Lehre KP Rolstad B Danbolt NC A monoclonal antibody raised against an [Na.+K.] coupled L-glutamate transporter purified from rat brain confirms glial localization. Fed Eur Biochem Soc Lett 1993 317 79 84 7679083
  61. Li Y Zhou Y Danbolt NC The rates of postmortem proteolysis of glutamate transporters differ dramatically between cells and between transporter subtypes. J Histochem Cytochem 2012 60 11 811 21 22859703 PMC3524567
  62. Lin CL Tzingounis AV Jin L Furuta A Kavanaugh MP Rothstein JD Molecular cloning and expression of the rat EAAT4 glutamate transporter subtype. Brain Res Mol Brain Res 1998 63 1 174 9 9838098
  63. Lozovaya NA Grebenyuk SE Tsintsadze T Feng B Monaghan DT Krishtal OA Extrasynaptic NR2B and NR2D subunits of NMDA receptors shape 'superslow' afterburst EPSC in rat hippocampus. J Physiol 2004 558 451 463 15146049 PMC1664978
  64. Maragakis NJ Dykes-Hoberg M Rothstein JD Altered expression of the glutamate transporter EAAT2b in neurological disease. Ann Neurol 2004 55 469 477 15048885
  65. Marcaggi P Attwell D Short- and long-term depression of rat cerebellar parallel fibre synaptic transmission mediated by synaptic crosstalk. J Physiol 2007 578 545 550 17110417 PMC2075140
  66. Marsman A van den Heuvel MP Klomp DW Kahn RS Luijten PR Hulshoff Pol HE Glutamate in schizophrenia: a focused review and meta-analysis of (1)H-MRS studies. Schizophr Bull 2013 1 120 129 21746807 PMC3523901
  67. 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 2008 511 2 155 72 18770868
  68. Matute C Ransom BR Roles of white matter in central nervous system pathophysiologies. ASN Neuro 2012 4 2 89 101 PMC3310305 22313331
  69. Melone M Bellesi M Conti F Synaptic localization of GLT-1a in the rat somatic sensory cortex. Glia 2009 57 1 108 17 18720407
  70. Melone M Bellesi M Ducati A Lacoangeli M Conti F Cellular and Synaptic Localization of EAAT2a in Human Cerebral Cortex. Front Neuroanat 2011 14 4 151 21258616 PMC3024003
  71. Mennerick S Dhond RP Benz A Xu W Rothstein JD Dandolt NC Isenberg KE Zorumski CF Neuronal expression of the glutamate transporter GLT-1 in hippocampal microcultures. J Neurosci 1998 18 4490 4499 9614226 PMC6792702
  72. Milton ID Banner SJ Ince PG Piggott NH Fray AE Thatcher N Horne CH Shaw PJ Expression of the glial glutamate transporter EAAT2 in the human CNS: an immunohistochemical study. Brain Res Mol Brain Res 1997 52 1 17 31 9450673
  73. Minelli A Barbaresi P Reimer RJ Edwards RH Conti F The glial glutamate transporter GLT-1is localized both in the vicinity of and at distance from axon terminals in the rat cerebral cortex. Neuroscience 2001 108 151 159 11738130
  74. Montana V Ni Y Sunjara V Hua X Parpura V Vesicular glutamate transporter-dependent glutamate release from astrocytes. J Neurosci 2004 24 11 2633 2642 15028755 PMC6729507
  75. Northington FJ Traystman RJ Koehler RC Martin LJ GLT1, glial glutamate transporter, is transiently expressed in neurons and develops astrocyte specificity only after midgestation in the ovine fetal brain. J Neurobiol 15 1999 39 4 515 526 10380073
  76. O'Kane RL Martinez-Lopez I DeJoseph MR Jr Hawkins RA Na(1)-dependent glutamate transporters (EAAT1, EAAT2, and EAAT3) of the blood–brain barrier. A mechanism for glutamate removal. J Biol Chem 1999 274 31891 5 10542215
  77. O'Shea RD Roles and regulation of glutamate transporters in the central nervous system. Clin Exper Pharmacol Physiol 2002 29 1018 1023 12366395
  78. Ottersen OP Zhang N Walberg F Metabolic compartmentation of glutamate and glutamine: morphological evidence obtained by quantitative immunocytochemistry in rat cerebellum. Neuroscience 1992 46 3 519 34 1347649
  79. Ota M Ishikawa M Sato N Hori H Sasayama D Hattori K Teraishi T Nakata Y Kunugi H Glutamatergic changes in the cerebral white matter associated with schizophrenic exacerbation. Acta Psychiatr Scand 2012 126 1 72 78 22432602
  80. Palmieri F The mitochondrial transporter family (SLC25): physiological and pathological implications. Pflugers Arch 2004 447 5 689 709 14598172
  81. Parpura V Grubiši V Verkhratsky A Ca(2+) sources for the exocytotic release of glutamate from astrocytes. Biochim Biophys Acta 2011 1813 5 984 91 21118669
  82. Pines G Danbolt NC Bjoras M Zhang Y Bendahan A Eide L Koepsell H Storm-Mathisen J Seebert E Kanner B Cloning and expression of a rat brain L-glutamate transporter. Nature 1992 360 464 467 1448170
  83. Pitt D Nagelmeier IE Wilson HC Raine CS Glutamate uptake by oligodendrocytes: Implications for excitotoxicity in multiple sclerosis. Neurology 2003 61 8 1113 1120 14581674
  84. Pow DV Barnett NL Changing patterns of spatial buffering of glutamate in developing rat retinae are mediated by the Müller cell glutamate transporter GLAST. Cell Tissue Res 1999 1 57 66 10398883
  85. Proper EA Hoogland G Kappen SM Jansen GH Rensen MG Schrama LH van Veelen CW van Rijen PC van Nieuwenhuizen O Gispen WH de Graan PN Distribution of glutamate transporters in the hippocampus of patients with pharmaco-resistant temporal lobe epilepsy. Brain 2002 125 Pt 1 32 43 11834591
  86. Rauen T Wiessner M Sullivan R Lee A Pow DV A new GLT1 splice variant: cloning and immunolocalization of GLT1c in the mammalian retina and brain. Neurochem Int 2004 5 7 1095 1106 15337309
  87. Regan MR Huang YH Kim YS Dykes-Hoberg MI Jin L Watkins AM Bergles DE Rothstein JD Variations in promoter activity reveal a differential expression and physiology of glutamate transporters by glia in the developing and mature CNS. J Neurosci 2007 27 6607 6619 17581948 PMC6672708
  88. Reye P Sullivan R Fletcher EL Pow DV Distribution of two splice variants of the glutamate transporter GLT1 in the retinas of humans, monkeys, rabbits, rats, cats and chickens. J Comp Neurol 2002a 445 1 12 11891650
  89. Reye P Sullivan R Pow DV Distribution of two splice variants of the glutamate transporter GLT-1 in the developing rat retina. J Comp Neurol 2002b 447 4 323 330 11992519
  90. Reye P Sullivan R Scott H Pow DV Distribution of two splice variants of the glutamate transporter GLT-1 in rat brain and pituitary. Glia 2002c 38 3 246 255 11968062
  91. Ritter SL Asay MJ Paquet M Paavola KJ Reiff RE Yun CC Hall RA GLAST Stability and Activity Are Enhanced by Interaction with the PDZ Scaffold NHERF-2. Neurosci Lett 2011 487 3 7 20430067 PMC2923238
  92. Roberts RC Roche JK McCullumsmith R The localization of the excitatory amino acid transporters EAAT1 and EAAT2 in human postmortem cortex: A light and electron microscopic study. Program No. 899.02/HH16. Neuroscience Meeting Planner 2011 Society for Neuroscience Washington, DC PMC4164610 25064059
  93. Rothstein JD Dykes-Hoberg M Pardo CA Bristol LA Jin L Kuncl RW Kanai Y Hediger MA Wang Y Schielke JP Welty DF Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate. Neuron 1996 16 675 686 8785064
  94. Rothstein JD Martin L Levey AI Dykes-Hoberg M Jin L Wu D Nash N Kuncl RW Localization of neuronal and glial transporters. Neuron 1994 13 713 725 7917301
  95. Rothstein JD van Kammen M Levey AI Martin LJ Kunel RW Selective loss of glial glutamate transporter GLT-l in amyotrophic lateral sclerosis. Ann Neural 1995 38 73 84 7611729
  96. Rusakov DA Kullmann DM Extrasynaptic glutamate diffusion in the hippocampus: ultrastructural constraints, uptake, and receptor activation. J Neurosci 1998 18 9 3158 70 9547224 PMC6792642
  97. Salt TE Eaton SA Turner JP Characterization of the metabotropic glutamate receptors (mGluRs) which modulate GABA-mediated inhibition in the ventrobasal thalamus. Neurochem Internatl 1996 29 3 317 322 8885291
  98. Schmitt A Asan E Puschel B Jons T Kugler P Expression of the glutamate transporter GLTI in neuronal cells of the rat central nervous system: non-radioactive in situ hybridization and comparative immunocytochemistry. Neuroscience 1996 71 989 1004 8684627
  99. Schmitt A Asan E Lesch KP Kugler P A splice variant of glutamate transporter GLT1/EAAT2 expressed in neurons: cloning and localization in rat nervous system. Neuroscience 2002 109 45 61 11784699
  100. Shan D Lucas EK Drummond JB Haroutunian V Meador-Woodruff JH McCullumsmith RE Abnormal expression of glutamate transporters in temporal lobe areas in elderly patients with schizophrenia. Schizophr Res 2013 144 1-3 1 8 23356950 PMC3572263
  101. Shan D Mount D Moore S Haroutunian V Meador-Woodruff JH McCullumsmith RE Abnormal partitioning of hexokinase 1 suggests disruption of a glutamate transport protein complex in schizophrenia. Schizophr Res 20 2 2014 pii: S0920-9964(14)00051-6. doi: 10.1016/j.schres.2014.01.028. [Epub ahead of print] PMC4151500 24560881 · DOI
  102. Shan D Yates S Roberts RC McCullumsmith RE Update on the Neurobiology of Schizophrenia: a Role for Extracellular Microdomains. MINERVA PSICHIATA 2012 53 233 49 PMC3783347 24077131
  103. Sibson NR Dhankhar A Mason GF Behar KL Rothman DL Shulman RG In vivo 13C NMR measurements of cerebral glutamine synthesis as evidence for glutamate-glutamine cycling. Proc Natl Acad Sci USA 1997 94 6 2699 704 9122259 PMC20152
  104. Spat A Fulop L Koncz P Szanda G When is high-Ca+ microdomain required for mitochondrial Ca+ uptake? Acta Physiologica 2009 195 1 139 47 18983456
  105. Storck T Schulte S Hofmann K Stoffel W Structure, expression, and functional analysis of a Na -dependent glutamate/ aspartate transporter from rat brain. Proc NatI Acad Sci USA 1992 89 10955 10959 PMC50461 1279699
  106. Storm-Mathisen J Iversen LL Uptake of [3H] glutamic acid in excitatory nerve endings: light and electron microscopic observations in the hippocampal formation of the rat. Neuroscience 1979 4 1237 1253 492534
  107. Storm-Mathisen J Wold JE In vivo high-affinity uptake and axonal transport of D-[2,3-3H]aspartate in excitatory neurons. Brain Res 1981 230 1-2 427 33 6172187
  108. Sullivan SM Macnab ST Bjorkman ST Coldizt PB Pow DV GLAST1b, the exon-9 skipping form of the glutamate-aspartate transporter EAAT1 is a sensitive marker of neuronal dysfunction in the hypoxic brain. Neuroscience 2007 149 434 45 17869431
  109. Szabadkai G Rizzuto R Chaperones as parts of organelle networks. Adv Exp Med Biol 2007 594 64 77 17205676
  110. 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 1997 276 1699 1702 9180080
  111. Taxt T Storm-Mathisen J Uptake of D-aspartate and L-glutamate in excitatory axon terminals in hippocampus: autoradiographic and biochemical comparison with gamma-aminobutyrate and other amino acids in normal rats and in rats with lesions. Neuroscience 1984 11 79 100 6143283
  112. Torp R Danbolt NC Babaie E Bjoras M Seeberg E Storm-Mathisen J Ottersen OP Differential expression of two glial glutamate transporters in the rat brain: an in situ hybridization study. Eur J Neurosci 1994 6 936 942 7952280
  113. Torp R Hoover F Danbolt NC Storm-Mathisen J Ottersen OP Differential distribution of the glutamate transporters GLT1 and EAAC1 in rat cerebral cortex and thalamus: an in situ hybridization analysis. Anat Embryol (Berl) 1997 195 4 317 326 9108197
  114. Tsvetkov E Shin RM Bolshakov VY Glutamate uptake determines pathway specificity of long-term potentiation in the neural circuitry of fear conditioning. Neuron 2004 41 139 51 14715141
  115. Tzingounis AV Wadiche JI Glutamate transporters: confining runaway excitation by shaping synaptic transmission. Nat Rev Neurosci 2007 8 12 935 47 17987031
  116. Utsunomiya-Tate N Endou H Kanai Y Tissue specific variants of glutamate transporter GLT-1. FEBS Lett 1997 416 312 316 9373176
  117. Velaz-Faircloth M McGraw TS Malandro MS Fremeau RT Jr Kilberg MS Anderson K Characterization and distribution of the neuronal glutamate transporter EAACI in rat brain. Am J Physiol 1996 270 C67 C75 8772431
  118. Vallejo-Illarramendi A Domercq M Pérez-Cerdá F Ravid R Matute C Increased expression and function of glutamate transporters in multiple sclerosis. Neurobiol Dis 2006 21 154 64 16061389
  119. Watase K Hashimoto K Kano M Yamada K Watanabe M Inoue Y Okuyama S Sakagawa T Ogawa S Kawashima N Hori S Takimoto M Wada K Tanaka K Motor discoordination and increased susceptibility to cerebellar injury in GLAST mutant mice. Eur J Neurosci 1998 10 3 976 88 9753165
  120. Weng HR Chen JH Pan ZZ Nie H Glial glutamate transporter 1 regulates the spatial and temporal coding of glutamatergic synaptic transmission in spinal lamina II neurons. Neuroscience 2007 149 898 907 17935889
  121. Williams SM Sullivan RK Scott HL Finkelstein DI Colditz PB Lingwood BE Dodd PR Pow DV Glial glutamate transporter expression patterns in brains from multiple mammalian species. Glia 2005 49 4 520 541 15578656
  122. Xu NJ Bao L Fan HP Bao GB Pu L Lu YJ Wu CF Zhang X Pei G Morphine withdrawal increases glutamate uptake and surface expression of glutamate transporter GLT1 at hippocampal synapses. J Neurosci 2003 23 4775 4784 12805317 PMC6740794

Cited by

Sorted by citations

Authors
Roberts, R. C., Roche, J. K., & McCullumsmith, R. E.
Affiliations
  • University of Alabama at Birmingham (US)
  • University of Cincinnati (US)
Corresponding author
  • Roberts, R.C.
  • McCullumsmith, R.E.
ORCID
Venue
Neuroscience
Publisher
Elsevier BV
Published
2014-09
Volume
277
Pages
522-540
ISSN
0306-4522 (ISSN-L)
DOI
10.1016/j.neuroscience.2014.07.019
PMC
PMC4164610
OpenAlex
W1971043748
Cited by
76
References
1
Citations by year
2026: 4 · 2025: 1 · 2024: 5 · 2023: 4 · 2022: 10 · 2021: 3 · 2020: 6 · 2019: 12 · 2018: 8 · 2017: 8 · 2016: 6 · 2015: 8 · 2014: 1
FWCI
3.22
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Mental Health (R01MH094445, MH087752, MH094445, R21MH087752, MH074016, K08MH074016)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
glutamate transporters, GLAST, GLT-1, glutamate uptake, glutamate spillover, astrocytes, prefrontal cortex, postmortem brain, glutamatergic synapses, hypoxia, postmortem interval, electron microscopy
MeSH terms
Adult, Aged, Animals, Astrocytes, Female, Humans, Male, Microscopy, Electron, Middle Aged, Neurons, Species Specificity, Prefrontal Cortex, Mice, Knockout, Excitatory Amino Acid Transporter 1, Excitatory Amino Acid Transporter 2, Glutamate Plasma Membrane Transport Proteins

About these checks

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

Statistics and arithmetic are recomputed, not judged.

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

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

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