Excitatory amino acid transporters as emerging targets for central nervous system therapeutics

Bibliography

• FONNUM F: Neurochemical studies on glutamate-mediated neurotransmission. In: Excitatory Amino Acids. Meldrum BS, Moroni F, Simon RO, Woods JH (Eds.), Raven Press Ltd., New York, USA (1990:15–25.
   Google Scholar
• HAYASHI T: Effects of sodium glutamate on the nervous system. Keio J. Med (1954) 3:183–192.
   Google Scholar
• •First demonstration of excitatory properties of glutamate.
   Google Scholar
• CURTIS DR, PHILLIS J, WATKINS JC: The chemical excita-tion of spinal neurons. Nature (1959) 183:611–612.
   PubMed Web of Science ®Google Scholar
• DINGLEDINE R, BORGES K, BOWIE D, TRAYNELIS SF: Theglutamate receptor ion channels. Pharmacol. Rev. (1999) 51:7–61.
   PubMed Web of Science ®Google Scholar
• STORM-MATHISEN J, DANBOLT NC, OTTERSEN OP:Localization of glutamate and its membrane transport proteins. In: CNS Neurotransmitters and Neuromodulators: Glutamate. Stone TW (Ed.), CRC Press, Boca Raton, USA (1995):1–18.
   Google Scholar
• HOLT WF: Glutamate in health and disease: the role of inhibitors. In: Neuroprotection in CNS Diseases. Bar PR, Beal MF (Eds.), Marcel Dekker, Inc., New York, USA (1997):87–119.
   Google Scholar
• FONNUM F, HASSEL B: Glutamate synthesis, metabo-lism, and uptake. In: CNS Neurotransmitters and Neuromodulators: Glutamate. Stone TW (Ed.), CRC Press, Boca Raton, USA (1995):19–34.
   Google Scholar
• NICHOLLS DG: The release of glutamate from synaptic terminals. In: CNS Neurotransmitters and Neuromodula-tors: Glutamate. Stone TW (Ed.), CRC Press, Boca Raton, USA (1995):35–52.
   Google Scholar
• TRUSSELL L: Control of time course of glutamatergic synaptic currents. Prog. Brain Res. (1998) 116:59–69.
   PubMedGoogle Scholar
• OTIS TS, WU Y-C, TRUSSELL LO: Delayed clearance oftransmitter and the role of glutamate transporters at synapses with multiple release sites. J. Neurosci. (1996) 16:1634–1644.
   PubMedGoogle Scholar
• BARBOUR B, KELLER BU, LLANO I, MARTY A: Prolongedpresence of glutamate during excitatory synaptic transmission to cerebellar Purkinje cells. Neuron (1994) 12:1331–1343.
   PubMed Web of Science ®Google Scholar
• SARANTIS M, BALLERINI L, MILLER B et al.: Glutamate uptake from the synaptic cleft does not shape the decay of the non-NMDA component of the synaptic current. Neuron (1993) 11:541–549.
   PubMedGoogle Scholar
• ISAACSON JS, NICOLL RA: The uptake inhibitor L-trans-PDC enhances responses to glutamate but fails to alter the kinetics of excitatory synaptic currents in the hippocampus. j Neurophysiol. (1993) 70:2187–2191.
   PubMedGoogle Scholar
• TONG G, JAHR CE: Block of glutamate transporters potentiates postsynaptic excitation. Neuron (1994) 13:1195–1203.
   PubMedGoogle Scholar
• ASZTELY F, ERDEMLI G, KULLMANN DM: Extrasynapticglutamate spillover in the hippocampus: dependence on temperature and the role of active glutamate uptake. Neuron (1997) 18:281–93.
   PubMed Web of Science ®Google Scholar
• ENGELSEN BA, MYRSETH E, BORGMANN R.: Altera-tions in excitatory amino acid transmitters in human neurological disease and neuropathology. In: Neurotoxicity of Excitatory Amino Acids. Guidotti A (Ed.), Raven Press Ltd., New York, USA (1990):311–332.
   Google Scholar
• INCE PG, EGGETT CJ, SHAW PJ: The role of excitotox-icity in neurological disease. Res. Contemp. Pharmaco-ther. (1997) 8:195–212.
   Google Scholar
• •Comprehensive review discussing excitotoxic mechanisms.
   Google Scholar
• MELDRUM BS: The glutamate synapse as a therapeutical target: perspective for the future. Prog. Brain Res. (1998) 116:441–458.
   PubMedGoogle Scholar
• OLNEY JW, IKONOMIDOU C: Excitotoxic mechanisms operative in youth and old age. In: Neurobiology of the NMDA Receptor From Chemistry to the Clinic. Kozikowski AP (Ed.) ACH Publishers, Inc., New York, USA (1991) :187–202.
   Google Scholar
• BAR-PELED O, ROTHSTEIN JD: Anti-glutamate therapies for neurodegenerative disease: the case for amyotrophic lateral sclerosis. In: Cell Death and Diseases of the Nervous System. Koliatsos VE, Ratan RR (Eds.), Humana Press, Totowa, NJ, USA (1999):633–647.
   Google Scholar
• LOGAN WJ, SNYDER SH: Unique high affinity uptake systems for glycine, glutamic and aspartic acids in central nervous tissue of the rat. Nature (1971) 234:297–299.
   PubMed Web of Science ®Google Scholar
• •First report of high affinity glutamate uptake in brain.
   Google Scholar
• BALCAR VJ, JOHNSTON GAR: The structural specificityof the high affinity uptake of L-glutamate and L-aspartate by rat brain slices. J. Neurochem. (1972) 19:2657–2666.
   PubMedGoogle Scholar
• BENNETT JP, LOGAN WJ, SNYDER SH: Amino acid neurotransmitter candidates: sodium-dependent high-affinity uptake by a unique synaptosomal fraction. Science (1972) 178:997–999.
   PubMedGoogle Scholar
• NICHOLLS D, ATTWELL D: The release and uptake of excitatory amino acids. Trends Pharmacol Sci. (1990) 11:462–468.
   PubMed Web of Science ®Google Scholar
• •An excellent early review describing properties of glutamate uptake systems.
   Google Scholar
• SCHOUSBOE A: Transport and metabolism of glutamate and GABA in neurons and glial cells. Int. Rev. Neurobiol (1981) 22:1–45.
   PubMedGoogle Scholar
• FERKANY J, COYLE JT: Heterogeneity of sodium-dependent excitatory amino acid uptake mechanisms in rat brain. J. Neurosci. Res. (1986) 16:491–503.
   PubMedGoogle Scholar
• ROBINSON MB, HUNTER-ENSOR M, SINOR J: Pharmaco-logically distinct sodium-dependent t-[3H]glutamate transport processes in rat brain. Brain Res. (1991) 544:196–202.
   PubMedGoogle Scholar
• STORCK T, SCHULTE S, HOFMANN K, STOFFEL W: Structure, expression, and functional analysis of a Natclependent glutamate/aspartate transporter from rat brain. Proc. Natl. Acad. Sci. USA (1992) 89:10955–10959.
   PubMed Web of Science ®Google Scholar
• •Describes the cloning of GLAST subtype.
   Google Scholar
• PINES G, DANBOLT NC, BJORAS M et al.: Cloning and expression of a rat brain 1.-glutamate transporter. Nature (1992) 360:464–467.
   PubMed Web of Science ®Google Scholar
• •Covers the cloning of GLT-1 subtype.
   Google Scholar
• KANAI Y, HEDIGER MA: Primary structure and functional characterization of a high-affinity glutamate transporter. Nature (1992) 360:467–471.
   PubMed Web of Science ®Google Scholar
• •Discusses the cloning of EAAC1 subtype.
   Google Scholar
• ARRIZA JL, FAIRMAN WA, WADICHE JI et al.: Functional comparisons of three glutamate transporter subtypes cloned from human cortex. J. Neurosci. (1994) 14:5559–5569.
   PubMed Web of Science ®Google Scholar
• •Describes the cloning of EAAT human homologues.
   Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• ARRIZA JL, ELIASOF S, KAVANAUGH MP, AMARA SG: Excitatory amino acid transporter 5, a retinal glutamate transporter coupled to a chloride conduc-tance. Proc. Natl. Acad. Sci. USA (1997) 94:4155–4160.
   PubMed Web of Science ®Google Scholar
• WAHLE S, STOFFEL W: Membrane topology of the high-affinity 1.-glutamate transporter (GLAST-1) of the central nervous system. J. Cell Biol. (1996) 135:1867–1877.
   PubMedGoogle Scholar
• SEAL RP, AMARA SG: A reentrant loop domain in the glutamate carrier EAAT1 participates in substrate binding and translocation. Neuron (1998) 21:1487–1498.
   PubMedGoogle Scholar
• GRUNEWALD M, BENDAHAN A, KANNER BI: Biotinyla-tion of single cysteine mutants of the glutamate transporter GLT-1 from rat brain reveals its unusual topology. Neuron (1998) 21:623–632.
   PubMedGoogle Scholar
• ROBINSON MB, DOWD LA: Heterogeneity and functional properties of subtypes of sodium-dependent glutamate transporters in the mammalian central nervous system. Adv. Pharmacol. (1997) 37:69–115.
   PubMedGoogle Scholar
• •Review focusing on glutamate transporter function in native systems.
   Google Scholar
• GEGELASHVILI G, SCHOUSBOE A: Cellular distribution and kinetic properties of high-affinity glutamate transporters. Brain Res. Bull. (1998) 43 (3):233–238.
   Google Scholar
• •Discussion of functional properties of cloned glutamate transporters.
   Google Scholar
• SEAL RP, AMARA SG: Excitatory amino acid transporters: a family in flux. Ann. Rev. Pharmacol Toxicol (1999) 39:431–456.
   PubMed Web of Science ®Google Scholar
• •Review on structural and ionic properties of glutamate transporters.
   Google Scholar
• YAMADA H, YATSUSHIRO S, YAMAMOTO A et al: Functional expression of a GLT-1 type Natclependent glutamate transporter in rat pinealocytes. J. Neurochem. (1997) 69:1491–1498.
   PubMedGoogle Scholar
• VANDENBERG RJ: Molecular pharmacology and physiology of glutamate transporters in the central nervous system. Clin. Exp. Pharmacol. Physiol. (1998) 25:383–400.
   PubMedGoogle Scholar
• DANBOLT NC, CHAUDHRY FA, DEHNES Y et al.: Proper-ties and localization of glutamate transporters. Prog. Brain Res. (1998) 116:23–43.
   PubMed Web of Science ®Google Scholar
• •Review focusing on detailed localisation of glutamate transporters.
   Google Scholar
• ROTHSTEIN JD, MARTIN L, LEVEY Al et al.: Localizationof neuronal and glial glutamate transporters. Neuron (1994) 13:713–725.
   PubMed Web of Science ®Google Scholar
• TORP R, DANBOLT NC, BABAIE E et al.: Differentialexpression of two glial glutamate transporters in the rat brain: An in situ hybridization study. Eur. Neurosci. (1994) 6:936–942.
   PubMedGoogle Scholar
• LEHRE KP, LEVY LM, OTTERSEN OP et al: Differentialexpression of two glial glutamate transporters in the rat brain: quantitative and immunocytochemical observations. J. Neurosci. (1995) 15:1835–1853.
   PubMedGoogle Scholar
• KIRSCHNER MA, COPELAND NG, GILBERT DJ et al.:Mouse excitatory amino acid transporter EAAT2: Isolation, characterization, and proximity to neuroex-citability loci on mouse chromosome 2. Genomics (1994) 24:218–224.
   PubMedGoogle Scholar
• NAKAYAMA T, KAWAKAMI H, TANAKA K, NAKAMURA S:Expression of three glutamate transporter subtype mRNAs in human brain regions and peripheral tissues. Mol. Brain Res. (1996) 36:189–192.
   PubMedGoogle Scholar
• BERGER UV, HEDIGER MA: Comparative analysis of glutamate transporter expression in rat brain using differential double in situ hybridization. Anat. Embriml. (1998) 198:13–30.
   PubMedGoogle Scholar
• MILTON ID, BANNER SJ, INCE PG et al.: Expression of theglial glutamate transporter EAAT2 in the human CNS: an immunohistochemical study. Mol Brain Res. (1997) 52:17–31.
   PubMedGoogle Scholar
• KANAI Y, BHIDE PG, DIFIGLIA M, HEDIGER MA:Neuronal high-affinity glutamate transport in the rat central nervous system. NeuroReport (1995) 6:2357–2362.
   PubMed Web of Science ®Google Scholar
• VELAZ-FAIRCLOTH M, MCGRAW TS, MALANDRO MS et.al.: Characterization and distribution of the neuronal glutamate transporter EAAC1 in rat brain. Am. J. Pharmacol. (1996) 270:C67–75.
   Google Scholar
• SHASHIDHARAN P, HUNTLEY GW, MURRAY JM et al:Immunohistochemical localization of the neuron-specific glutamate transporter EAAC1 (EAAT3) in rat brain and spinal cord revealed by a novel monoclonal antibody. Brain Res. (1997) 773:138–148.
   Google Scholar
• TORP R, HOOVER F, DANBOLT NC et al: Differentialdistribution of the glutamate transporters GLT1 and rEAAC1 in rat cerebral cortex and thalamus: An in situ hybridization analysis. Anat. Embryo]. (1997) 195:317–326.
   PubMedGoogle Scholar
• FURUTA A, MARTIN LJ, UN CL et al.: Cellular andsynaptic localization of the neuronal glutamate transporters excitatory amino acid transporter 3 and 4. Neuroscience (1997) 81:1031–1042.
   PubMedGoogle Scholar
• DEHNES Y, CHAUDHRY FA, ULLENSVANG K et al.: Theglutamate 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) 18:3606–3619.
   PubMedGoogle Scholar
• KANAI Y, TROTTI D, NUSSBERGER S, HEDIGER MA: The high-affinity glutamate transporter family: structure, function, and physiological relevance. In: Contempo-rary Neuroscience: Neurotransmitter Transporters: Structure, Function, and Regulation. Reith MEA (Ed.), Humana Press, Totowa, New Jersey, USA (1997):171–213.
   Google Scholar
• KIRYU S, YAOGL, MORITA N et al.: Nerve injury enhances rat neuronal glutamate transporter expres-sion: Identification by differential display PCR. J. Neurosci. (1995) 15:7872–7878.
   PubMedGoogle Scholar
• YAMACHITA T, KOHMURA E, YUGUCHI T et al: Changes in glutamate/aspartate transporters (GLAST/G1uT-1) mRNA expression following facial nerve transection. Mol Brain Res. (1996) 38:294–299.
   PubMedGoogle Scholar
• LEVY LM, LEHRE KP, WALAAS SI et al.: Down-regulation of glial glutamate transporters after glutamatergic denervation in the rat brain. Eur. J. Neurosci. (1995) 7:2036–2041.
   PubMed Web of Science ®Google Scholar
• SUTHERLAND ML, DELANEY TA, NOEBELS JL: Glutamatetransporter mRNA expression in proliferative zones of the developing and adult murine CNS. J. Neurosci. (1996) 16:2191–2207.
   PubMedGoogle Scholar
• SHIBATA T, WATANABE W, TANAKA K, WADA K, INOUEY: Dynamic changes in expression of glutamate transporter mRNAs in developing brain. NeuroReport (1996) 7:705–709.
   PubMedGoogle Scholar
• YAMADA K, WATANABE M, SHIBATA T et al.: Glutamatetransporter GLT-1 is transiently localised on growing axons of the mouse spinal cord before establishing astrocytic expression. J. Neurosci. (1998) 18:5706–5713.
   PubMedGoogle Scholar
• FURUTA A, ROTHSTEIN JD, MARTIN LJ: Glutamate transporter protein subtypes are expressed differen-tially during rat CNS development. J. Neurosci. (1997) 17:8363–8375.
   PubMedGoogle Scholar
• ULLENSVANG K, LEHRE KP, STORM-MATHISEN J, DANBOLT NC: Differential developmental expression of the two rat brain glutamate transporter proteins GLAST and GLT. Eur. J. Neurosci. (1997) 9:1646–1655.
   PubMedGoogle Scholar
• BAR-PELED O, BEN-HUR H, BIEGON A et al.: Distribution of glutamate transporter subtypes during human brain development. J. Neurochem. (1997) 69:2571–2580.
   PubMed Web of Science ®Google Scholar
• ITOH M, WATANABE Y, WATANABE M et.al.: Expression of a glutamate transporter subtype, EAAT4, in the developing human cerebellum. Brain Res. (1997) 767:265–271.
   PubMedGoogle Scholar
• INAGE YW, ITCH M, WADA K, TAKASHIMA S: Expressionof two glutamate transporters, GLAST and EAAT4, in the human cerebellum: their correlation in develop-ment and neonatal hypoxic-ischemic damage. J. Neuropathol. Exp. Neurol. (1998) 57:554–562.
   PubMedGoogle Scholar
• CHAUDHURY F, LEHRE KP, VAN LOOKEREN M et al.:Glutamate transporters in glial plasma membranes: highly differentiated localization revealed by quantita-tive ultrastructural immunocytochemistry. Neuron (1995) 15:711–720.
   PubMedGoogle Scholar
• SCHMITT A, ASAN E, PUSCHEL B, KUGLER P: Cellular andregional distribution of the glutamate transporter GLAST in the CNS of rats: nonradioactive in situ hybridization and comparative immunocytochem-istry. j Neurosci. (1997) 17:1–10.
   PubMedGoogle Scholar
• MENNERICK S, DHOND RP, BENZ A et al.: Neuronalexpression of the glutamate transporter GLT-1 in hippocampal microcultures. J. Neurosci. (1998) 18:4490–4499.
   PubMedGoogle Scholar
• CONTI F, DEBIASI S, MINELLI A, ROTHSTEIN JD, MELONE M: EAAC1, a high-affinity glutamate transporter, is localised to astrocytes and gabaergic neurones besides pyramidal cells in the rat cerebral cortex. Cerebral Cortex (1998) 8:108–116.
   PubMedGoogle Scholar
• LEHRE KP, DANBOLT NC: The number of glutamate transporter subtype molecules at glutamatergic synapses: chemical and stereological quantification in young adult rat brain. J. Neurosci. (1998) 18:8751–8757.
   PubMed Web of Science ®Google Scholar
• RAUEN T, ROTHSTEIN JD, WASSLE H: Differential expression of three glutamate transporter subtypes in the rat retina. Cell Tissue Res. (1996) 286:325–336.
   PubMed Web of Science ®Google Scholar
• CHOI I, CHIU SY: Expression of high-affinity neuronal and glial glutamate transporters in the rat optic nerve. Glia (1997) 20:184–192.
   PubMedGoogle Scholar
• ELIASOF S, ARRIZA JL, LEIGHTON BH et al.: Excitatory amino acid transporters of the salamander retina: identification, localization, and function. J. Neurosci. (1998) 18:698–712.
   PubMedGoogle Scholar
• DUNLOP J, MCILVAIN HB, LOU Z, FRANCO R: The pharmacological profile of 1.-glutamate transport in human NT2 neurones is consistent with excitatory amino acid transporter 2. Eur. J. Pharmacol (1998) 360:249–256.
   PubMedGoogle Scholar
• TAN J, ZELENAIA O, CORREALE D, ROTHSTEIN JD, ROBINSON MB: Expression of the GLT-1 subtype of Nat-dependent glutamate transporter: pharmacol-ogical characterization and lack of regulation by protein kinase C. J. Pharm. Exp. Ther. (1999) 289:1600–1610.
   PubMedGoogle Scholar
• VANDENBERG RJ, MITROVIC AD, CHEBIB M, BALCAR VJ,JOHNSTON GA: Contrasting modes of action of methylglutamate derivatives on the excitatory amino acid transporters, EAAT1 and EAAT2. Mol. Pharmacol. (1997) 51:809–815.
   PubMedGoogle Scholar
• SHIMAMOTO K, LEBRUN B, YASUDA-KAMATANI Y et al:DL-threo-beta-benzyl-oxyaspartate, a potent blocker of excitatory amino acid transporters. Mol. Pharmacol. (1998) 53:195–201.
   PubMed Web of Science ®Google Scholar
• BRIDGES RJ, STANLEY MS, ANDERSON MW, COTMAN CW, CHAMBERLIN AR: Conformationally defined neurotransmitter analogues. Selective inhibition of glutamate uptake by one pyrrolidine-2,4- dicarboxy-late diastereomer. J. Med. Chem. (1991) 34:717–725.
   PubMedGoogle Scholar
• BRIDGES RJ, LOVERING FE, KOCH H, COTMAN CW, CHAMBERLIN AR: A conformationally constrained competitive inhibitor of the sodium-dependent glutamate transporter in forebrain synaptosomes: t-anti-endo-3,4-methanopyrrolidine dicarboxylate. Neurosci. Lett. (1994) 174:193–197.
   PubMedGoogle Scholar
• NAKAMURA Y, KATAOKA K, ISHIDA M, SHINOZAKI H:(25,35,4R)-2-(carboxycyclopropyfiglycine, a potent and competitive inhibitor of both glial and neuronal uptake of glutamate. Neuropharmacology (1993) 32:833–837.
   PubMedGoogle Scholar
• BRIDGES RJ, KAVANAUGH MP, CHAMBERLIN AR: A pharmacological review of competitive inhibitors and substrates of high-affinity, sodium-dependent glutamate transport in the central nervous system. Curr. Pharm. Des. (1999) 5:363–379.
   PubMed Web of Science ®Google Scholar
• •Essential reading for in-depth review of the current pharma-cology of EAATs.
   Google Scholar
• KANNER BI, SCHULDINER S: Mechanism of transportand storage of neurotransmitters. CRC Grit. Rev. Biochem. (1987) 22:1–38.
   Google Scholar
• ERECINSKA M: The neurotransmitter amino acid transport systems. A fresh outlook on an old problem. Biochem. Pharmacol. (1987) 36:3547–55.
   PubMedGoogle Scholar
• KANNER BI, SHARON I: Active transport oft-glutamateby membrane vesicles isolated from rat brain. Biochemistry (1978) 17:3949–3953.
   PubMed Web of Science ®Google Scholar
• SZATKOWSKI M, BARBOUR B, ATTWELL D: The potassium-dependence of excitatory amino acid transport: resolution of a paradox. Brain Res. (1991) 555:343–345.
   PubMedGoogle Scholar
• ATTWELL D, BARBOUR B, SZATKOWSKI M: Nonvesicularrelease of neurotransmitter. Neuron (1993) 11:401–407.
   PubMed Web of Science ®Google Scholar
• STALLCUP WB, BULLOCH K, BAETGE EE: Coupled transport of glutamate and sodium in a cerebellar nerve cell line. J. Neurochem. (1979) 32:57–65.
   PubMed Web of Science ®Google Scholar
• BARBOUR B, BREW H, ATTWELL D: Electrogenic glutamate uptake in glial cells is activated by intracel-lular potassium. Nature (1988) 335:433–435.
   PubMed Web of Science ®Google Scholar
• ELIASOF S, WERBLIN F: Characterization of theglutamate transporter in retinal cones of the tiger salamander. J. Neurosci. (1993) 13:402–411.
   PubMed Web of Science ®Google Scholar
• ZERANGUE N, KAVANAUGH MP: Flux coupling in a neuronal glutamate transporter. Nature (1996) 383:634–637.
   PubMed Web of Science ®Google Scholar
• LEVY LM, WARR O, ATTWELL D: Stoichiometry of the glial glutamate transporter GLT-1 expressed inducibly in a Chinese hamster ovary cell line selected for low endogenous Natdependent glutamate uptake. J. Neurosci. (1998) 18:9620–9628.
   PubMed Web of Science ®Google Scholar
• OTIS TS, JAHR CE: Anion currents and predicted glutamate flux through a neuronal glutamate transporter. J. Neurosci. (1998) 18:7099–7110.
   PubMedGoogle Scholar
• WADICHE JI, KAVANAUGH MP: Macroscopic and microscopic properties of a cloned glutamate transporter/chloride channel. J. Neurosci. (1998) 1 8:7650–7661.
   Google Scholar
• BERGLES DE, JAHR CE: Synaptic activation of glutamatetransporters in hippocampal astrocytes. Neuron (1997) 1 9:1297–1308.
   Google Scholar
• ERECINSKA M, WANTORSKY D, WILSON DF: Aspartatetransport in synaptosomes from rat brain. J. Biol. Chem. (1983) 258:9069–9077.
   PubMedGoogle Scholar
• NELSON PJ, DEAN GE, ARONSON PS, RUDNICK G: Hydrogen ion cotransport by the renal brush border glutamate transporter. Biochemistry (1 9 8 3) 22:5459 5463.
   Google Scholar
• WADICHE JI, VANDENBERG RJ, ARRIZA JL, AMARA SG,KAVANAUGH MP: Ligand-gated chloride conductance associated with a human glutamate transporter. Biophys. J. (1995) 68:A437.
   Google Scholar
• WADICHE JI, AMARA SG, KAVANAUGH MP: Ion fluxes associated with excitatory amino acid transport. Neuron (1995) 15:721–728.
   PubMedGoogle Scholar
• BILLUPS B, ROSSI D, ATTWELL D: Anion conductance behavior of the glutamate uptake carrier in salamander retinal glial cells. J. Neurosci. (1996) 16:6722–6731.
   PubMedGoogle Scholar
• OTIS TS, KAVANAUGH MP, JAHR CE: Postsynaptic glutamate transport at the climbing fiber-Purkinje cell synapse. Science (1997) 277:1515–1518.
   PubMedGoogle Scholar
• ELIASOF S, JAHR CE: Retinal glial cell transporter is coupled to an anionic conductance. Proc. Natl. Acad. ScL USA (1996) 93:4153–4158.
   PubMed Web of Science ®Google Scholar
• PICAUD SA, LARSSON HP, WELLIS DP, LECAR H, WERBLIN FS: Cone photoreceptors respond to their own glutamate release in the tiger salamander. Proc. Natl. Acad. ScL USA (1995) 92:9417–9421.
   PubMed Web of Science ®Google Scholar
• GRANT GB, DOWLING JE: A glutamate-activated chloride current in cone-driven ON bipolar cells of the white perch retina. J. NeuroscL (1995) 15:3852–3862.
   PubMedGoogle Scholar
• SCHWARTZ EA, TACHIBANA M: Electrophysiology of glutamate and sodium co-transport in a glial cell of the salamander retina. J. Physiol. (1990) 426:43–80.
   PubMed Web of Science ®Google Scholar
• VANDENBERG RJ, ARRIZA JL, AMARA SG, KAVANAUGH MP: Constitutive ion fluxes and substrate binding domains of human glutamate transporters. J. Biol. Chem. (1995) 270:17668–17671.
   PubMedGoogle Scholar
• FAIRMAN WA, SONDERS MS, MURDOCH GH, AMARA SG: Arachidonic acid elicits a substrate-gated proton current associated with the glutamate transporter EAAT4. Nature NeuroscL (1998) 1:105–113.
   PubMedGoogle Scholar
• TZINGOUNIS AV, UN CL, ROTHSTEIN JD, KAVANAUGH MP: Arachidonic acid activates a proton conductance in the rat glutamate transporter EAAT4. J. Biol. Chem. (1998) 273:17315–17317.
   PubMedGoogle Scholar
• GEGELASHVILI G, CIVENNI G, RACAGNI G et al.: Glutamate receptor agonists up-regulate glutamate transporter GLAST in astrocytes. NeuroReport (1996) 8:261–265.
   PubMed Web of Science ®Google Scholar
• GEGELASHVILI G, DANBOLT NC, SCHOUSBOE A: Neuronal soluble factors differentially regulate the expression of the GLT-1 and GLAST glutamate transporters in cultured astroglia. j Neurochem. (1997) 69:2612–2615.
   PubMed Web of Science ®Google Scholar
• SWANSON RA, LIU J, MILLER JW et al.: Neuronal regula-tion of glutamate transporter subtype expression in astrocytes. j Neurosci. (1997) 17:932–940.
   Google Scholar
• SCHLAG BD, VONDRASEK JR, MUNIR M et al.: Regulation of the glial Nat-dependent glutamate transporters by cyclic AMP analogs and neurons. Mol. Pharmacol. (1998) 53:355–369.
   PubMed Web of Science ®Google Scholar
• CASADO M, BENDAHAN A, ZAFRA F et al.: Phosphoryla-tion and modulation of brain glutamate transporters by protein kinase C. J. Biol Chem. (1993) 268:27313–27317.
   PubMedGoogle Scholar
• GANEL R, CROSSON CE: Modulation of human glutamate transporter activity by phorbol ester. J. Neurochem. (1998) 70:993–1000.
   PubMedGoogle Scholar
• CONRADT M, STOFFEL W: Inhibition of the high-affinity brain glutamate transporter GLAST-1 via direct phosphorylation. J. Neurochem. (1 99 7) 68:1244 1251.
   Google Scholar
• DOWD LA, ROBINSON MB: Rapid stimulation of EAAC1-mediated Natclependent L-glutamate transport activity in C6 glioma cells by phorbol ester. J. Neurochem. (1996) 67:508–516.
   PubMedGoogle Scholar
• DAVIES KE, STRAFF DJ, WEINSTEIN EA et al: Multiple signaling pathways regulate cell surface expression and activity of the excitatory amino acid carrier 1 subtype of Glu transporter in C6 glioma. J. NeuroscL (1998) 18:2475–2485.
   PubMedGoogle Scholar
• ZERANGUE N, ARRIZA JL, AMARA SG, KAVANAUGH MP: Differential modulation of human glutamate transporter subtypes by arachidonic acid. J. Biol. Chem. (1995) 270:6433–6435.
   PubMedGoogle Scholar
• •First report of AA enhancement of EAAT2 activity.
   Google Scholar
• VOLTERRA A, TROTTI D, CASSUTTI P et al.: High sensitivity of glutamate uptake to extracellular free arachidonic acid levels in rat cortical synaptosomes and astrocytes. j Neurochem. (1992) 59:600–606.
   PubMed Web of Science ®Google Scholar
• TROTTI D, VOLTERRA A, LEHRE KP et al: Arachidonic acid inhibits a purified and reconstituted glutamate transporter directly from the water phase and not via the phospholipid membrane. J. Biol. Chem. (1995) 270:9890–9895.
   PubMedGoogle Scholar
• SPIRIDON M, KAMM D, BILLUPS B, MOBBS P, ATTWELL D: Modulation by zinc of the glutamate transporters in glial cells and cones isolated from the tiger salamander retina. J. Physiol (1998) 506:363–376.
   PubMedGoogle Scholar
• VANDENBERG RJ, MITROVIC AD, JOHNSTON GA: Molecular basis for differential inhibition of glutamate transporter subtypes by zinc ions. Mol Pharmacol (1998) 54:189–196.
   PubMedGoogle Scholar
• FAIRMAN WA, VANDENBERG RJ, AMARA SG: Modulation of the excitatory amino acid transporters EAAT1-5 by zinc. Soc. NeuroscL Abstr. (1998) 24:2072.
   Google Scholar
• TROTTI D, DANBOLT NC, VOLTERRA A: Glutamate transporters are oxidant-vulnerable: a molecular link between oxidative and excitotoxic neurodegenera-tion. Trends Pharmacol. Sci. (1998) 19:328–334.
   PubMed Web of Science ®Google Scholar
• •Comprehensive review linking oxidative damage to impaired glutamate transporter function.
   Google Scholar
• BERMAN SB, HASTINGS TG: Inhibition of glutamate transport in synaptosomes by dopamine oxidation and reactive oxygen species. J. Neurochem. (1997) 69:1185–1195.
   PubMed Web of Science ®Google Scholar
• LIPTON SA, ROSENBERG PA: Mechanisms of disease: excitatory amino acids as a common pathway for neurologic disorders. New Engl. J. Med. (1994) 330:613–622.
   PubMed Web of Science ®Google Scholar
• •A seminal review.
   Google Scholar
• COYLE JT, PUTTFARCKEN P: Oxidative stress, glutamate and neurodegenerative disease. Science (1993) 262:689–695.
   PubMed Web of Science ®Google Scholar
• •A seminal review.
   Google Scholar
• MASSIEU L, GARCIA O: The role of excitotoxicity and metabolic failure in the pathogenesis of neurological disorders. Neurobiol. (1998) 6:99–108.
   PubMedGoogle Scholar
• BILLUPS B, ROSSI D, OSHIMA T et al.: Physiological and pathological operation of glutamate transporters. Prog. Brain Res. (1998) 116:45–57.
   PubMed Web of Science ®Google Scholar
• TAKAHASHI M, BILLUPS B, ROSSI D et al.: The role of glutamate transporters in glutamate homeostasis in the brain. J. Exp. Biol. (1997) 200:401–409.
   PubMed Web of Science ®Google Scholar
• IKONOMIDOU C, TURSKI L: Neurodegenerative disorders: Clues from glutamate and energy metabo-lism. Crit. Rev. Neurobiol. (1996) 10:239–263.
   PubMedGoogle Scholar
• ROTHSTEIN JD: Excitotoxicity and neurodegeneration in amyotrophic lateral sclerosis. Clin. Neurosci. (1996) 3:348–359.
   Google Scholar
• •Discusses the glutamatergic hypothesis and its relationship to ALS.
   Google Scholar
• MASLIAH E, ALFORD M, DETERESA R et al.: Deficient glutamate transport is associated with neurodegenera-tion in Alzheimer's disease. Ann. Neurol. (1996) 40:759–766.
   PubMed Web of Science ®Google Scholar
• MURRAY AM, SHANNON WEICKERT C, SHASHIDHARAN P, HYDE TM, KLEINMAN JE: Decreased neuron-specific excitatory amino acid transporter 3 (EAAT3) in schizo-phrenic hippocampus. Soc. Neurosci. Abstr. (1996) 22:1680.
   Google Scholar
• SCHNEIDER JS, WADE T, LIDSKY TI: Chronic neuroleptic treatment alters expression of glial glutamate transporter GLT-1 mRNA in the striatum. NeuroReport (1998) 9:133–136.
   PubMedGoogle Scholar
• ROTHMAN SM: Synaptic release of excitatory amino transmitter mediates anoxic neuronal death. J. Neurosci. (1984) 4:1884–1891.
   PubMed Web of Science ®Google Scholar
• CHOI DW: Excitotoxic cell death. J. Neurobiol. (1992) 23:1261–1276.
   PubMedGoogle Scholar
• PALMER AM: Excitatory amino acid neurons and receptors in Alzheimer's disease. In: Neurobiology of the NMDA Receptor: From Chemistry to the Clinic. Kozikowski AP (Ed.), VCH Publishers, Inc., New York, USA (1990:203–237.
   Google Scholar
• •Review of the pathological role of glutamate in Alzheimer's disease.
   Google Scholar
• ROSENBERG PA, AIZENMAN E: Hundred-fold increase in neuronal vulnerability to glutamate toxicity in astrocyte-poor cultures of a rat cerebral cortex. Neurosci. Lett. (1989) 103:162–168.
   PubMed Web of Science ®Google Scholar
• •First report suggesting the role of glial transport in neuroprotection.
   Google Scholar
• FREUND WD, GRIESHOP B, NEUMAN U, REDDIG S: Glutamate-induced calcium responses in rat primary cortical cultures are potentiated by co-administration of glutamate transport inhibitors. Neurosci. Lett. (1995) 188:61–64.
   PubMedGoogle Scholar
• MCBEAN GJ, ROBERTS PJ: Neurotoxicity of 1.-glutamate and DL-threo-3-hydroxyaspartate in the rat striatum. J. Neurochem. (1985) 44:247–254.
   PubMedGoogle Scholar
• ROBINSON MD, DJALI S, BUCHHALTER JR: Inhibition of glutamate uptake with t-trans-pyrrolidine-2,4, -dicarboxylate potentiates glutamate toxicity in primary hippocampal cultures. J. Neurochem. (1993) 61:2099–2103.
   PubMedGoogle Scholar
• ROTHSTEIN JD, JIN L, DYKES-HOBERG M, KUNCL RW: Chronic glutamate uptake inhibition produces a model of slow neurotoxicity. Proc. Natl. Acad. ScL USA (1993) 90:6591–6595.
   PubMed Web of Science ®Google Scholar
• VORNOV JJ, TASKER RC, PARK J: Neurotoxicity of acute glutamate transport blockade depends on coactivation of both NMDA and AMPA/kainate receptors in organo-typic hippocampal cultures. Exp. Neurol. (1995) 133:7–17.
   PubMedGoogle Scholar
• WANG GI, CHUNG HJ, SCHNUER JA et al.: Dihydrokainate-sensitive neuronal glutamate transport is required for protection of rat cortical neurons in culture against synaptically released glutamate. Eur.J. Neurosci. (1998) 10:2523–2531.
   PubMedGoogle Scholar
• ROTHSTEIN JD, DYKES-HOBERG M, PARDO CA et al.: Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate. Neuron (1996) 16:675–686.
   PubMed Web of Science ®Google Scholar
• •First in vivo demonstration that glial transporters are necessary for neuronal survival.
   Google Scholar
• TANAKA K, WATASE K, MANABE T et al.: Epilepsy and exacerbation of brain injury in mice lacking the glutamate transporter GLT-1. Science (1997) 267:1699–1702.
   Google Scholar
• •Covers GLT-1 knock out.
   Google Scholar
• SUTHERLAND M: The role of glutamate transport in seizure-induced excitotoxic cell death: A new transgenic model. Epilepsia (1998) 39\(Supp1.6):62.
   Google Scholar
• •First report of neuroprotective effect of GLT-1 overexpression.
   Google Scholar
• WATASE K, HASHIMOTO K, KANO M et al.: Motor discoordination and increased susceptibility to cerebellar injury in GLAST mutant mice. Eur. J. Neurosci. (1998) 10:976–988.
   PubMedGoogle Scholar
• •Discusses GLAST knock out.
   Google Scholar
• PEGHINI P, JANSEN J, STOFFEL W: Glutamate transporter EAAC-1-deficient mice develop dicarbox-ylic aminoaciduria and behavioural abnormalities but no neurodegeneration. EMBO J (1997) 16:3822–3832.
   PubMed Web of Science ®Google Scholar
• •Details EAAC1 knock out.
   Google Scholar
• SHAYAKUL C, KANAI Y, LEE WS et al.: Localization of the high-affinity glutamate transporter EAAC1 in rat kidney. Am. J. Physiol. (1997) 273:F1023–1029.
   Google Scholar
• CHOI DW, ROTHMAN SM: The role of glutamate neurotoxicity in hypoxy-ischaemic neuronal death. Ann. Rev. Neurosci. (1990) 13:177–182.
   Google Scholar
• SZATKOWSKI M, ATTWELL D: Triggering and execution of neuronal death in brain ischaemia: Two phases of glutamate release by different mechanisms. Trends Neurosci. (1994) 17:359–365.
   PubMed Web of Science ®Google Scholar
• BULLOCK R, ZAUNER A, WOODWARD J, YOUNG HF: Massive persistent release of excitatory amino acids following human stroke. Stroke (1995) 26:2187–2189.
   PubMedGoogle Scholar
• CASTILLO J, DAVALOS A, NOYA M: Progression of ischaemic stroke and excitotoxic amino acids. Lancet (1997) 349:79–83.
   PubMed Web of Science ®Google Scholar
• FOSTER AC, FAGG GE: Neurobiology: taking apart NMDA receptors. Nature (1987) 329:395–396.
   PubMed Web of Science ®Google Scholar
• CHOI DW: Ionic dependence of glutamate neurotox-icity. j Neurosci. (1987) 7:369–379.
   PubMed Web of Science ®Google Scholar
• DUGAN LL, CHOI DW: Excitotoxicity, free radicals and cell membrane changes. Ann. Neurol (1994) 35:S17–S21.
   Google Scholar
• NICOTERA P, LIPTON SA: Excitotoxins in neuronal apoptosis and necrosis. J. Cereb. Blood Flow Metab. (1999) 19:583–591.
   PubMed Web of Science ®Google Scholar
• LEE JM, ZIPFEL GJ, CHOI DW: The changing landscape of ischaemic brain injury mechanisms. Nature (1999) 399:A7–A14.
   PubMed Web of Science ®Google Scholar
• DREJER J, BENVENISTE H, DIEMER NH, SCHOUSBOE A: Cellular origin of ischemia-induced glutamate release from brain tissue in vivo and in vitro. J. Neurochem. (1985) 45:145–151.
   PubMedGoogle Scholar
• WAHL F, OBRENOVITCH TP, HARDY A et al.: Altered glutamatergic transmission in neurological disorders: from high extracellular glutamate to excessive synaptic efficacy. Prog. Neurobiol. (1997) 51:39–87.
   PubMedGoogle Scholar
• SZATOWSKI M, BARBOUR B, ATTWELL D: Non-vesicular release of glutamate from glial cells by reversed electrogenic glutamate uptake. Nature (1990) 348:443–446.
   PubMedGoogle Scholar
• LONGUEMARE MC, SWANSON RA: Excitatory amino acid release from astrocytes during energy failure by reversal of sodium-dependent uptake. J. Neurosci. Res. (1995) 40:379–385.
   PubMedGoogle Scholar
• GEMBA T, OSHIMA T, NINOMIYA M: Glutamate efflux via the reversal of the sodium-dependent glutamate transporter caused by glycolytic inhibition in rat cultured astrocytes. Neuroscience (1994) 63:789–795.
   PubMedGoogle Scholar
• ROETTGER V, LIPTON P: Mechanism of glutamate release from rat hippocampal slices during in vitro ischemia. Neuroscience (1996) 75:677–685.
   PubMedGoogle Scholar
• KOCH HP, CHAMBERLAIN AR, BRIDGES RJ: Non-transportable inhibitors attenuate reversal of glutamate uptake in synaptosomes following a metabolic insult. Mol Pharmacol. (1999) 55:1044–1048.
   PubMedGoogle Scholar
• PHYLLIS JW, SMITH-BARBOUR M, PERKINS LM, ()REGAN MH: Characterisation of glutamate, aspartate and GABA release from ischaemic rat cerebral cortex. Brain Res. Bull. (1994) 34:457–466.
   PubMedGoogle Scholar
• DAWSON LA, DJALI S, GONZALES C, VINEGRA MA, ZALESKA MM: Characterization of transient focal ischemia-induced increases in extracellular glutamate and aspartate: contribution of reversal of the GLT-1 transporter. J. Neurochem. (1999) Submitted.
   Google Scholar
• SEKI Y, FEUSTEL J, KELLER RW, TRANMER BI, KIMELBERG HK: Inhibition of ischemia-induced glutamate release in rat striatum by dihydrokainate and an anion channel blocker. Stroke (1999) 30:433–440.
   PubMedGoogle Scholar
• OTORI Y, SHIMADA S, TANAKA K et al.: Marked increase in glutamate-aspartate transporter (GLAST/GluT-1) mRNA following transient retinal ischemia. Mol. Brain R. (1994) 27:310–314.
   PubMedGoogle Scholar
• HARADA T, HARADA C, MATANABE M et al: Functions of the two glutamate transporters GLAST and GLT-1 in the retina. Proc. Natl. Acad. ScL USA (1998) 95:4663–4666.
   PubMedGoogle Scholar
• FUJITA H, SATO K, WEN T-C, PENG Y, SAKANAKA M: Differential expressions of glycine transporter 1 and three glutamate transporter mRNA in the hippocampus of gerbils with transient forebrain ischemia. j Cereb. Blood Flow Metab. (1999) 19:604–615.
   PubMed Web of Science ®Google Scholar
• TORP R, LEKIEFFRE D, LEVY LM et al.: Reduced postischemic expression of a glial glutamate transporter, GLT1, in the rat hippocampus. Exp. Brain Res. (1995) 103:51–58.
   PubMed Web of Science ®Google Scholar
• YAN YP, YIN KJ, SUN FY: Effect of glutamate transporter on neuronal damage induced by photochemical thrombotic brain ischemia. NeuroReport (1998) 9:441–446.
   PubMedGoogle Scholar
• FADEN Al, DEMEDIUK P, PANTER SS, VINK R: The role of excitatory amino acids and NMDA receptors in traumatic brain injury. Science (1989) 244:798–800.
   PubMed Web of Science ®Google Scholar
• KATOH H, SIMA K, NAWASHIRO H, WADA K, CHIGASAKI H: The effect of MK-801 on extracellular neuroactive amino acids in hippocampus after closed head injury followed by hypoxia in rats. Brain Res. (1997) 758:731–769.
   Google Scholar
• MCINTOSH TK, JUHLER M, WIELOD T: Novel pharma-cologic strategies in the treatment of experimental traumatic brain injury. J. Neurotrauma (1998) 15:731–769.
   PubMed Web of Science ®Google Scholar
• ALLESANDRI B, BULLOCK R: Glutamate and its receptors in the pathophysiology of brain and spinal cord injuries. Prog. Brain Res. (1998) 116:303–330.
   PubMedGoogle Scholar
• PALMER AM, MARION DW, BOTSCHELLER ML, SWEDLOW PE, STYREN SD, DEKOSKY ST: Traumatic brain injury-induced excitotoxicity assessed in a controlled cortical impact model. J. Neurochem. (1993) 61:2015–2024.
   PubMed Web of Science ®Google Scholar
• GLOBUS NYT, ALONSO O, DIETRICH WD, BUSTO R, GINSBERG MD: Glutamate release and free radical production following brain injury: effects of posttrau-matic hypothermia. J. Neurochem. (1995) 65:1704–1711.
   PubMedGoogle Scholar
• KATAYAMA V, BECKER DP, TAMURA T, HOVADA DA: Massive increases in extracellular potassium and the indiscriminate release of glutamate following concus-sive brain injury. J. Neurosurg. (1990) 73:889–900.
   PubMed Web of Science ®Google Scholar
• KOURA SS, DOPPENBERG EMR, MARMAROU A et al.: Relationship between excitatory amino acid release and outcome after severe human head injury. Acta Neurochir. (1998) 71:244–246.
   Google Scholar
• PALMER AM, MARION DW, BOTSCHELLER ML, BOWEN DM, DEKOSKY ST: Increased transmitter amino acids concentrations in human ventricular CSF after brain trauma. NeuroReport (1994) 6:153–156.
   PubMed Web of Science ®Google Scholar
• BULLOCK R, ZAUNER A, MYSEROS JS et al.: Evidence for prolonged release of excitatory amino acids in severe human head trauma-relationship to clinical events. Ann. NY Acad. ScL (1995) 11:290–298.
   Google Scholar
• ZAUNER A, BULLOCK R: The role of excitatory amino acids in severe brain trauma: opportunities for therapy: a review. J. Neurotrauma (1995) 12:547–554.
   PubMed Web of Science ®Google Scholar
• RAO VLR, BASKAYA M, DOGAN A, ROTHSTEIN JD, DEMPSEY RJ: Traumatic brain injury down-regulates glial glutamate transporter (GLT-1 and GLAST) proteins in rat brain. J. Neurochem. (1998) 70:2020–2027.
   PubMedGoogle Scholar
• •First report demonstrating altered levels of glutamate transporter after TB1
   Google Scholar
• MA X, XIA Y, YAN HQ et al: Increased expression of neuronal glutamate transporter protein (EAAC1) after traumatic brain injury (TEO in rats. J. Neurotrauma (1998) 15:882.
   Google Scholar
• BENDER AS, NORENBERG MD: Effect of trauma on cell volume and glutamate uptake in cultured astrocytes. J. Neurotrauma (1998) 15:858.
   Google Scholar
• SULLIVAN PG, KELLER JN, MATTSON MP, SCHEFF SW: Traumatic brain injury alters synaptic homeostasis: implications for impaired mitochondrial and transport function. J. Neurotrauma (1998) 15:789–798.
   PubMed Web of Science ®Google Scholar
• TENG Y, WRATHALL J: Local blockade of sodium channels by tetrodotoxin ameliorates tissue loss and long-term functional deficits resulting from experi-mental spinal cord injury. J. Neurosci. (1997) 17:4359–4366.
   PubMed Web of Science ®Google Scholar
• STYS PK: Anoxic and ischemic injury of myelinated axons in CNS white matter: from mechanistic concepts to therapeutics. J. Cereb. Blood Flow Metab. (1998) 18:2–25.
   PubMed Web of Science ®Google Scholar
• LI S, MEALING GAR, MORLEY P, STYS PK: Novel injury mechanism in anoxia and trauma of spinal cord white matter: Glutamate release via reverse Na+-dependent glutamate transport. J. Neurosci. (1999) 19:1–9.
   PubMedGoogle Scholar
• BEAL MF: Does impairment of energy metabolism result in excitotoxic neuronal death in neurodegen-erative disease? Ann. Neurol (1992) 31:119–130.
   Web of Science ®Google Scholar
• NOVELLI A, REILLY JA, LYSKO PC, HENNEBERRY RC: Glutamate becomes neurotoxic via the NMDA receptor when intracellular energy levels are reduced. Brain Res. (1988) 451:205–212.
   PubMed Web of Science ®Google Scholar
• •First experimental report demonstrating excitotoxic cellular injury as a process which is secondary to a reduction in energy status.
   Google Scholar
• SCHOR NF: Inactivation of mammalian brain glutamic synthetase by oxygen radicals. Brain Res. (1988) 456:17–21.
   PubMed Web of Science ®Google Scholar
• SANCHEZ-CARBENTE MD, MASSIEU L: Transient inhibi-tion of glutamate uptake in vivo induces neurodegen-eration when energy metabolism is impaired. J. Neurochem. (1999) 72:129–138.
   PubMedGoogle Scholar
• ROSEN DR, SIDDIGUE T, PATTERSON D et al: Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature (1993) 362:59–62.
   PubMed Web of Science ®Google Scholar
• PLAITAKIS A, CONSTANTAKAKIS E, SMITH J: The neuroexcitotoxic amino acids glutamate and aspartate are altered in the spinal cord and brain in amyotrophic lateral sclerosis. Ann. Neurol. (1988) 24:446–449.
   PubMed Web of Science ®Google Scholar
• SHAW PJ, FORREST V, INCE PG, RICHARDSON JP, WASTELL HJ: CSF and plasma amino acid levels in motor neuron disease: Elevation of CSF glutamate in a subset of patients. Neurodegeneration (1995) 4:209–216.
   PubMedGoogle Scholar
• ROTHSTEIN JD, MARTIN LJ, KUNCL RW: Decreased glutamate transport by the brain and spinal cord in amyotrophic lateral sclerosis. New Engl. J. Med. (1992) 326:1464–1468.
   PubMed Web of Science ®Google Scholar
• ROTHSTEIN JD, VANKAMMEN M, LEVEY Al, MARTIN LJ, KUNCL RW: Selective loss of glial glutamate transporter GLT-1 amyotrophic lateral sclerosis. Ann. Neurol (1995) 38:73–84.
   PubMed Web of Science ®Google Scholar
• •First proposed link between loss of glial transporter and human motoneurone disease.
   Google Scholar
• BRISTOL LA, ROTHSTEIN JD: Glutamate transporter gene expression in amyotrophic lateral sclerosis motor cortex. Ann. Neurol (1996) 39:676–679.
   PubMed Web of Science ®Google Scholar
• LIN C-L G, BRISTOL LA, JIN L et al.: Aberrant RNA processing in a neurodegenerative disease: the cause for absent EAAT2, a glutamate transporter, in amyotrophic lateral sclerosis. Neuron (1 99 8) 20:589–602.
   Google Scholar
• WONG PC, ROTHSTEIN JD, PRICE DL: The genetic and molecular mechanisms of motor neuron disease. Curr. Opin. Neurobiol. (1998) 8:791–799.
   PubMed Web of Science ®Google Scholar
• PEDERSEN WA, FU W, KELLER JN et al.: Protein modifica-tion by the lipid peroxidation product 4-Hydroxynonenal in the spinal cords of amyotrophic lateral sclerosis patients. Ann. Neurol. (1998) 44:819–824.
   PubMed Web of Science ®Google Scholar
• TROTTI D, ROLFS A, DANBOLT NC, BROWN RH, JR., HEDIGER MA: SOD1 mutants linked to amyotrophic lateral sclerosis selectively inactivate a glial glutamate transporter. Nature Neurosci. (1999) 2:427–433.
   PubMed Web of Science ®Google Scholar
• ROTHSTEIN JD, KUNCL RW: Neuroprotective strategies in a model of chronic glutamate-mediated motor neuron toxicity. J. Neurochem. (1995) 65:643–651.
   PubMed Web of Science ®Google Scholar
• SCOTT HL, TANNENBERG AE, DODD PR: Variant forms of neuronal glutamate transporter sites in Alzheimer's disease cerebral cortex. J. Neurochem. (1 99 5) 64:2193-2202.
   Google Scholar
• LI S, MALLORY M, ALFORD M, TANAKA S, MASLIAH E: Glutamate transporter alterations in Alzheimer's disease are possibly associated with abnormal APP expression. J. Neuropathol. Exp. Neurol. (1997) 56:910–911.
   Google Scholar
• MASLIAH E: Mechanism of synaptic pathology in Alzheimer's disease. J. Neural. Transm. (1998) 53:147–158.
   Google Scholar
• BECKSTROM H, JULSRUD L, HAUGETO O et.al.: Interindi-vidual differences in the levels of the glutamate transporters GLAST and GLT, but no clear correlation with Alzheimer's disease. J. Neurosci. Res. (1999) 55:218–229.
   PubMed Web of Science ®Google Scholar
• GRAY CW, PATEL AJ: Neurodegeneration mediated by glutamate and 6-amyloid peptide: a comparison and possible interaction. Brain Res. (1995) 691:169–179.
   PubMed Web of Science ®Google Scholar
• HARRIS ME, WANG Y, PEDCIGO NW et al.: Amyloid 6-peptide (25-35) inhibits Natclependent glutamate uptake in rat hippocampal astrocyte cultures. J. Neurochem. (1996) 67:277–286.
   PubMed Web of Science ®Google Scholar
• HARRIS ME, CARNEY JM, COLE PS et al.: 6-amyloid peptide-derived, oxygen-dependent free radicals inhibit glutamate uptake in cultured astrocytes: implications for Alzheimer's disease. NeuroReport (1995) 6:1875–1879.
   PubMedGoogle Scholar
• •Postulated interaction between 13-amy1oid and glutamate uptake in Alzheimer's pathology.
   Google Scholar
• KELLER JN, PANG Z, GEDDES JW et al: Impairment of glucose and glutamate transport and induction of mitochondrial oxidative stress and dysfunction in synaptosomes by amyloid beta-peptide: role of the lipid peroxidation product 4-hydroxynonenal. J. Neurochem. (1997) 69:273–284.
   PubMed Web of Science ®Google Scholar
• MASLIAH E, MALLORY M, ALFORD M, TANAKA S, HANSEN LA: Caspase dependent DNA fragmentation might be associated with excitotoxicity in Alzheimer's disease. J. Neuropathol. Exp. Neurol. (1998) 57:1041–1052.
   PubMed Web of Science ®Google Scholar
• SUCHER NJ, LIPTON SA, DREYER EB: Molecular basis of glutamate toxicity in retinal ganglion cells. Vision Res. (1997) 37:3483–3493.
   PubMed Web of Science ®Google Scholar
• DREYER EB, ZURAKOWSKI D, SCHUMER RA, PODOS SM, LIPTON SA: Elevated glutamate levels in the vitreous body of humans and monkeys with glaucoma. Arch. Ophthalmol. (1996) 114:299–305.
   PubMed Web of Science ®Google Scholar
• RAUEN T, KANNER BI: Localization of the glutamate transporter GLT-1 in rat and macaque monkey retinae. NeuroscL Lett. (1994) 169:137–140.
   PubMed Web of Science ®Google Scholar
• DEROUICHE A, RAUEN T: Coincidence of L-glutamateh-aspartate transporter (GLAST) and glutamine synthetase (GS) immunoreactions in retinal glia: evidence for coupling of GLAST and GS in transmitter clearance. J. NeuroscL Res. (1995) 42:131–143.
   PubMed Web of Science ®Google Scholar
• SCHEYER RD: Involvement of glutamate in human epileptic activities. Prog. Brain Res. (1998) 116:359–370.
   PubMedGoogle Scholar
• JOHNSTON D, BROWN TH: Giant synaptic potential hypothesis for epileptiform activity. Science (1981) 211:294–297.
   PubMed Web of Science ®Google Scholar
• GODDARD GV, MCINTYRE, LEECH CK: A permanent change in brain function resulting from daily electrical stimulation. Exp. Neurol. (1969) 25:295–330.
   PubMed Web of Science ®Google Scholar
• JEFFERYS JGR, TRAUB RD: Electrophysiological substrates for focal epilepsies. Prog. Brain Res. (1998) 116:351–358.
   PubMedGoogle Scholar
• MASUKAWA LM, HIGASHIMA M, HART GJ, SPENCER DD, O'CONNOR MJ: NMDA receptor activation during epileptiform responses in the dentate gyrus of epileptic patients. Brain Res. (1991) 562:176–180.
   PubMedGoogle Scholar
• SHERWIN A, ROBITAILLE Y, QUESNEY F et al: Excitatory amino acids are elevated in human epileptic cerebral cortex. Neurology (1988) 38:920–923.
   PubMed Web of Science ®Google Scholar
• JANJUA NA, ITANO T, KUGOH T et al.: Familial increase in plasma glutamic acid in epilepsy. Epilepsy Res. (1992) 11:37–44.
   PubMedGoogle Scholar
• WILSON CL, MAIDMENT NT, SHOMER MH et al.: Comparison of seizure related amino acid release in human epileptic hippocampus versus a chronic, kainate rat model of hippocampal epilepsy. Epilepsy Res. (1996) 265:245–254.
   Google Scholar
• DURING NC, SPENCER DD: Extracellular hippocampal glutamate and spontaneous seizure in the conscious human brain. Lancet (1993) 341:1607–1610.
   PubMed Web of Science ®Google Scholar
• LOTHMAN WE, BENNETT JP, PERLIN JB: Alterations in neurotransmitter amino acids in hippocampal kindled seizures. Epilepsy Res. (1987) 1:313–320.
   PubMedGoogle Scholar
• JANJUA NA, KABUTO H, MORI A: Increased plasma glutamic acid in a genetic model of epilepsy. Neurochem. Res. (1992) 17:293–296.
   PubMedGoogle Scholar
• ZHANG WQ, HUDSON PM, SOBOTKA TJ, HONG JS, TILSON HA: Extracellular concentrations of amino acid transmitters in ventral hippocampus during and after the development of kindling. Brain. Res. (1991) 540:315–318.
   PubMedGoogle Scholar
• OBRENOVITCH TP, URENJAK J, ZILKHA E: Evidence disputing the link between seizure activity and high extracellular glutamate. J. Neurochem. (1996) 66:2446–2454.
   PubMedGoogle Scholar
• LEACH MJ, O'DONNELL RA, COLLINS KJ, MARDEN CM, MILLER AA: Effect of cortical kindling on rHID-aspartate uptake and glutamate metabolism in rats. Epilepsy Res. (1987) 1:145–148.
   PubMedGoogle Scholar
• OCONNOR ER, PIZZONIA JH, SPENCER DD, DE LANEROLLE NC: Glutamate, aspartate, and GABA transport in astrocytes cultured from human epileptic foci. Epilepsia (1996) 37 (Suppl. 5):51.
   Google Scholar
• SIMANTOV R, CRISPINO M, HOE W et al.: Changes in expression of neuronal and glial glutamate transporters in rat hippocampus following kainate-induced seizure activity. Ma Brain. Res. (1999) 65:112–123.
   Google Scholar
• YASHOR D, ZHU Z, ARMSTRONG DL Selective loss of EAAT2, a glial transporter, in CA1 and CA4 hippocampal subfields in Ammon's Horn Sclerosis. Epilesia (1996) 37 (Suppl. 5):213.
   Google Scholar
• TESSLER S, DANBOLT NC, FAULL RLM, STORM-MATHISEN J, EMSON PC: Expression of the glutamate transporters in human temporal lobe epilepsy. J. NeuroscL (1999) 88:1083–1091.
   Google Scholar
• AKBAR MT, TORP R, DANBOLT NC et al.: Expression of glial glutamate transporters GLT-1 and GLAST is unchanged in the hippocampus in fully kindled rats. Neuroscience (1997) 78:351–359.
   PubMedGoogle Scholar
• MILLER HP, LEVEY AI, ROTHSTEIN JD et al.: Alterations in glutamate transporter protein levels in kindling-induced epilepsy. J. Neurochem. (1997) 68:1564–1570.
   PubMed Web of Science ®Google Scholar
• SUTHERLAND ML, DELANEY TA, NOEBELS JL: Subtype-specific downregulation of glutamate transporter gene expression in three models of temporal lobe epilepsy. Epilepsia (1997) 38(Suppl.
   Google Scholar
• NONAKA M, KOHMURA E, YAMASHITA T et.al.: Increased transcription of glutamate-aspartate transporter (GLAST/G1uT-1) mRNA following kainic acid-induced limbic seizure. Brain Res. (1998) 55:54–60.
   Google Scholar
• ROGAWSKI MA: Excitatory amino acids and seizures. In: CNS Neurotransmitters and Neuromodulators: Glutamate. Stone TW (Ed.), CRC Press, Boca Raton, Florida, USA (1995):219–237.
   Google Scholar
• COYLE JT: The glutamatergic dysfunction hypothesis for schizophrenia. Harvard Rev. Psychiatry (1996) 3:241–253.
   PubMed Web of Science ®Google Scholar
• GOFF DC, WINE L: Glutamate in schizophrenia: clinical and research implications. Schiz. Res. (1997) 27:157–168.
   PubMedGoogle Scholar
• ARNOLD SE: Schizophrenia. In: Cell Death and Diseases of the Nervous System. Koliatsos VE, Ratan R. (Eds.), Humana Press, Totowa, NJ, USA (1999):527–541.
   Google Scholar
• TSAI G, PASSANI LA, SLUSHER BS et al.: Abnormal excita-tory neurotransmitter metabolism in schizophrenic brains. Arch. Gen. Psychiatry (1995) 52:829–836.
   PubMed Web of Science ®Google Scholar
• ISHIMARU M, KURAMAJI A, TORU M: Increases in strychnine-insensitive glycine binding sites in cerebral cortex of chronic schizophrenics: evidence for glutamate hypothesis. Biol. Psychiatry (1996) 35:84–95.
   Google Scholar
• KERKERIAN L, DUSTICIER N, NIEOULLON A: Modulatory effect of dopamine on high-affinity glutamate uptake in the rat striatum. J. Neurochem. (1987) 48:1301–1306.
   PubMedGoogle Scholar
• MAURA G, GIARDI A, RAITERI M: Release-regulating D-2 dopamine receptors are located on striatal glutama-tergic nerve terminals. J. Pharmacol Exp. Ther. (1988) 247:680–684.
   PubMedGoogle Scholar
• JEDEMA HP, MOGHADDAM B: Glutamatergic control of dopamine release during stress in the rat prefrontal cortex. J. Neurochem. (1994) 63:785–788.
   PubMed Web of Science ®Google Scholar
• MOGHADDAM B, ADAMS BW: Reversal of phencycli-dine effects by a group II metabotropic glutamate receptor agonist in rats. Science (1998) 281:1349–1352.
   PubMed Web of Science ®Google Scholar
• BACHUS SE, HYDE TM, SHANNON WEICKERT C, SHASHIDHARAN P, HERMAN MM, KLEINMAN JE: Reduced level of excitatory amino acid transporter 3 mRNA in hippocampus of schizophrenics. Soc. Neurosci. Abstr. (1996) 22:1680.
   Google Scholar
• OHNUMA T, AUGOOD SJ, ARAI H, MCKENNA PJ, EMSON PC: Expression of the human excitatory amino acid transporter 2 and metabotropic glutamate receptors 3 and 5 in the prefrontal cortex from normal individuals and patients with schizophrenia. Brain Res. Mol. Brain Res. (1998) 56:207–217.
   PubMedGoogle Scholar
• LIN CLG, JACKSON M, JIN L et al.: Identification and characterization of purkinje cell-specific glutamate transporter EAAT4 associated proteins (GTRAP4). Soc. Neurosi. Abstr. (1998) 24:2068.
   Google Scholar
• ORLOV I, UN CLG, SON W et al.: GTRAP3: identification and characterization of a neuronal transporter EAAC1-associated protein. Soc. Neurosi. Abstr. (1998) 24:2068.
   Google Scholar