• 1
    Balázs R., Machiyama Y., Hammond B.J., Julian T., Richter D. (1970) The operation of the gamma-aminobutyrate bypath of the tricarboxylic acid cycle in brain tissue in vitro.Biochem. J. 116,445461.
  • 2
    Battaglioli G. & Martin D.L. (1990) Stimulation of synaptosomal γ-aminobutyric acid synthesis by glutamate and glutamine. J. Neurochem. 54,11791187.
  • 3
    Battaglioli G. & Martin D.L. (1996) Glutamine stimulates γ-aminobutyric acid synthesis in synaptosomes but other putative astrocyte-to-neuron shuttle substrates do not. Neurosci. Lett. 209,129133.
  • 4
    Belhage B., Meier E., Schousboe A. (1986) GABA-agonists induce the formation of low-affinity GABA-receptors on cultured cerebellar granule cells via preexisting high affinity GABA-receptors.Neurochem. Res. 11,599606.
  • 5
    Belhage B., Hansen G.H., Meier E., Schousboe A. (1990) Effects of inhibitors of protein synthesis and intracellular transport on the γ-aminobutyric acid agonist-induced functional differentiation of cultured cerebellar granule cells. J. Neurochem. 55,11071113.
  • 6
    Belhage B., Hansen G.H., Schousboe A. (1993) Depolarization by K+ and glutamate activates different neurotransmitter release mechanisms in GABAergic neurons : vesicular versus non-vesicular release of GABA.Neuroscience 54,10191034.
  • 7
    Belhage B., Hansen G.H., Elster L., Schousboe A. (1998) Effects of gamma-aminobutyric acid (GABA) on synaptogenesis and synaptic function.Perspect. Dev. Neurobiol. 5,235246.
  • 8
    Bernasconi R., Maitre L., Martin P., Raschdorf F. (1982) The use of inhibitors of GABA-transaminase for the determination of GABA turnover in mouse brain regions : an evaluation of aminooxyacetic acid and gabaculine.J. Neurochem. 38,5766.
  • 9
    Borden L.A. (1996) GABA transporter heterogeneity : pharmacology and cellular localization.Neurochem. Int. 29,335356.
  • 10
    Breastrup C., Nielsen E.B., Sonnewald U., Knutsen L.J., Andersen K.E., Jansen J.A., Frederiksen K., Andersen P.H., Mortensen A., Suzdak P.D. (1990) (R)-N[4,4-Bis(3-methyl-2-thienyl)but-3-en-1-yl]nipecotic acid binds with high affinity to the brain γ-aminobutyric acid uptake carrier. J. Neurochem. 54,639647.
  • 11
    Bu D., Erlander M.G., Hitz B.C., Tillakaratne N.J.K., Kaufman D.L., Wagner-McPherson C.B., Evans B.A., Tobin A.J. (1992) Two human glutamate decarboxylases, 65-kDa GAD and 67-kDa GAD, are each encoded by a single gene.Proc. Natl. Acad. Sci. USA 89,21152119.
  • 12
    Carlson B.X., Elster L., Schousboe A. (1998) Pharmacological and functional implications of developmentally-regulated changes in GABA(A) receptor subunit expression in the cerebellum.Eur. J. Pharmacol. 352,114.
  • 13
    Cesar M. & Hamprecht B. (1995) Immunohistochemical examination of neural rat and mouse primary cultures using monoclonal antibodies raised against pyruvate carboxylase.J. Neurochem. 64,23122318.
  • 14
    Chapman A.G. & Evans M.C. (1983) Cortical GABA turnover during bicuculline seizures in rats.J. Neurochem. 41,886889.
  • 15
    De Mello F.G., Bachrach U., Nirenberg M. (1976) Ornithine and glutamate decarboxylase activities in developing chick retina.J. Neurochem. 27,847851.
  • 16
    Drejer J., Larsson O.M., Kvamme E., Svenneby G., Hertz L., Schousboe A. (1985) Ontogenetic development of glutamate metabolizing enzymes in cultured cerebellar granule cells and in cerebellum in vivo.Neurochem. Res. 10,4962.
  • 17
    During M.J., Ryder K.M., Spencer D.D. (1995) Hippocampal GABA transporter function in temporal-lobe epilepsy.Nature 376,174177.
  • 18
    Erlander M.G., Tillakaratne N.J.K., Feldblum S., Patel N., Tobin A.J. (1991) Two genes encode distinct glutamate decarboxylases.Neuron 7,91100.
  • 19
    Fink-Jensen A., Suzdak P.D., Swedberg M.D., Judge M.E., Hansen L., Nielsen P.G. (1992) The gamma-aminobutyric acid (GABA) uptake inhibitor, tiagabine, increases extracellular brain levels of GABA in awake rats.Eur. J. Pharmacol. 220,197201.
  • 20
    Gale K., Iadarola M.J., Casu M., Keating R.F. (1982) Relationship between GABA levels in vivo and anticonvulsant activity : importance of cellular compartments and regional localization in brain, inProblems in GABA Research from Brain to Bacteria (Okada Y. and Roberts E., eds), pp. 159181. Excerpta Medica, Amsterdam.
  • 21
    Garfinkel D. (1966) A simulation study of the metabolism and compartmentation in brain of glutamate, aspartate, the Krebs cycle, and related metabolites.J. Biol. Chem. 241,39183929.
  • 22
    Golan H. & Grossman Y. (1996) Block of glutamate decarboxylase decreases GABAergic inhibition at the crayfish synapses : possible role of presynaptic metabotropic mechanisms.J. Neurophysiol. 75,20892098.
  • 23
    Golan H., Talpalar A.E., Schleifstein-Attias D., Grossman Y. (1996) GABA metabolism controls inhibition efficacy in the mammalian CNS.Neurosci. Lett. 217,2528.
  • 24
    Gonzales C., Kaufman D.L., Tobin A.J., Chesselet M. -F. (1991) Distribution of glutamate decarboxylase (Mr 67,000) in the basal ganglia of the rat : an immunohistochemical study with a selective cDNA-generated polyclonal antibody.J. Neurocytol. 20,953961.
  • 25
    Gordon-Weeks P.R., Lockerbie R.O., Pearce B.R. (1984) Uptake and release of [3H]GABA by growth cones isolated from neonatal rat brain. Neurosci. Lett. 52,205210.
  • 26
    Gram L., Larsson O.M., Johnsen A.H., Schousboe A. (1988) Effects of valproate, vigabatrin and aminooxyacetic acid on release of endogenous and exogenous GABA from cultured neurons.Epilepsy Res. 2,8795.
  • 27
    Hassel B., Johannessen C.U., Sonnewald U., Fonnum F. (1998) Quantification of the GABA shunt and the importance of the GABA shunt versus the 2-oxoglutarate dehydrogenase pathway in GABAergic neurons.J. Neurochem. 71,15111518.
  • 28
    Henry S. & Tappaz M. (1991) Relative enrichment of the lighter 59 kDa form of glutamic acid decarboxylase in nerve endings : an immunoblotting study in pituitary neurointermediate lobe.Neurosci. Lett. 131,253256.
  • 29
    Hertz L. & Schousboe A. (1987) Primary cultures of GABAergic and glutamatergic neurons as model systems to study neurotransmitter functions. I. Differentiated cells, inModel Systems of Development and Aging of the Nervous System (Vernadakis A., Privat A., Lauder J. M., Timiras P. S., and Giacobini E., eds), pp. 1931. Martinus Nijhoff Publishing, Boston.
  • 30
    Hertz L., Yu A.C., Schousboe A. (1992) Uptake and metabolism of malate in neurons and astrocytes in primary cultures.J. Neurosci. Res. 33,289296.
  • 31
    Hokoc J.N., Ventura A.L., Gardino P.F., De Mello F.G. (1990) Developmental immunoreactivity for GABA and GAD in the avian retina : possible alternative pathway for GABA synthesis.Brain Res. 532,197202.
  • 32
    Iadarola M.J. & Gale K. (1980) Evaluation of increases in nerve terminal-dependent vs. nerve terminal-independent compartments of GABA in vivo.Brain Res. Bull. 5,S213S219.
  • 33
    Iadarola M.J. & Gale K. (1981) Cellular compartments of GABA in brain and their relationship to anticonvulsant activity.Mol. Cell. Biochem. 39,305330.
  • 34
    Kaufman D.L., McGinnes J.F., Krieger N.R., Tobin A.J. (1986) Brain glutamate decarboxylase cloned in λgt-11 : fusion protein produces γ-aminobutyric acid. Science 232,11381140.
  • 35
    Kaufman D.L., Houser C.R., Tobin A.J. (1991) Two forms of the γ-aminobutyric acid synthetic enzyme glutamate decarboxylase have distinct intraneuronal distributions and cofactor interactions. J. Neurochem. 56,720723.
  • 36
    Kihara M. & Kubo T. (1989) Aspartate aminotransferase for synthesis of transmitter glutamate in the medulla oblongata : effect of aminooxyacetic acid and 2-oxoglutarate.J. Neurochem. 52,11271134.
  • 37
    Kobayashi Y., Kaufman D.L., Tobin A.J. (1987) Glutamic acid decarboxylase cDNA : nucleotide sequence encoding an enzymatically active fusion protein.J. Neurosci. 7,27682772.
  • 38
    Kvamme E., Svenneby G., Torgner I.A. (1988) Glutaminases, inGlutamine and Glutamate in Mammals, Vol. 2 (Kvamme E., ed), pp. 5463. CRC Press, Boca Raton, Florida.
  • 39
    Laake J.H., Takumi Y., Eidet J., Torgner I.A., Roberg B., Kvamme E., Ottersen O.P. (1999) Postembedding immunogold labelling reveals subcellular localization and pathway-specific enrichment of phosphate activated glutaminase in rat cerebellum.Neuroscience 88,11371151.
  • 40
    Larsson O.M., Drejer J., Kvamme E., Svenneby G., Hertz L., Schousboe A. (1985) Ontogenetic development of glutamate and GABA metabolizing enzymes in cultured cerebral cortex interneurons and in cerebral cortex in vivo.Int. J. Dev. Neurosci. 3,177185.
  • 41
    Larsson O.M., Gram L., Schousboe I., Schousboe A. (1986) Differential effect of gamma-vinyl GABA and valproate on GABA-transaminase from cultured neurones and astrocytes.Neuropharmacology 25,617625.
  • 42
    Liden E., Karlson I., Sellstrom A. (1987) Is the concentration of γ-aminobutyric acid in the nerve terminal regulated via product inhibition of glutamic acid decarboxylase ? Neurochem. Res. 12,489493.
  • 43
    Martin D.L. & Rimvall K. (1993) Regulation of γ-aminobutyric acid synthesis in the brain. J. Neurochem. 60,395407.
  • 44
    Martin D.L., Martin S.B., Wu S.J., Espina N. (1991 a) Cofactor interactions and the regulation of glutamate decarboxylase activity. Neurochem. Res. 16,243249.
  • 45
    Martin D.L., Martin S.B., Wu S.J., Espina N. (1991 b) Regulatory properties of brain glutamate decarboxylase (GAD) : the apoenzyme of GAD is present principally as the smaller of two molecular forms of GAD in brain. J. Neurosci. 11,27252731.
  • 46
    Mason G.F., Gruetter R., Rothman D.L., Behar K.L., Shulman R.G., Novotny E.J. (1995) Simultaneous determination of the rates of the TCA cycle, glucose utilization, alpha-ketoglutarate/glutamate exchange, and glutamine synthesis in human brain by NMR.J. Cereb. Blood Flow Metab. 15,1225.
  • 47
    Matsuda T., Wu J., Roberts E. (1973) Electrophoresis of glutamic acid decarboxylase (EC from mouse brain in sodium dodecyl sulphate polyacrylamide gels.J. Neurochem. 21,167172.
  • 48
    McGeer E.G., McGeer P.L., Thompson S. (1983) GABA and glutamate enzymes, inGlutamine, Glutamate and GABA in the Central Nervous System (Hertz L., Kvamme E., McGeer E. G., and Schousboe A., eds), pp. 317. Alan R. Liss, Inc., New York.
  • 49
    Meier E., Hansen G.H., Schousboe A. (1985) The trophic effect of GABA on cerebellar granule cells is mediated by GABA-receptors.Int. J. Dev. Neurosci. 3,401407.
  • 50
    Meier E., Hertz L., Schousboe A. (1991) Neurotransmitters as developmental signals.Neurochem. Int. 19,115.
  • 51
    Minelli A., Brecha N.C., Karschin C., DeBiasi S., Conti F. (1995) GAT-1, a high-affinity GABA plasma membrane transporter, is localized to neurons and astroglia in the cerebral cortex.J. Neurosci. 15,77347746.
  • 52
    Nishimura M., Sato K., Mizuno M., Yoshiya I., Shimada S., Saito N., Tohyama M. (1997) Differential expression patterns of GABA transporters (GAT1-3) in the rat olfactory bulb.Brain Res. Mol. Brain Res. 45,268274.
  • 53
    Norenberg M.D. & Martinez-Hernandez A. (1979) Fine structural localization of glutamine synthetase in astrocytes of rat brain.Brain Res. 161,303310.
  • 54
    Patel A.J., Johnson A.L., Balázs R. (1974) Metabolic compartmentation of glutamate associated with the formation of γ-aminobutyrate. J. Neurochem. 23,12711279.
  • 55
    Paulsen R. & Fonnum F. (1987) Comparison of results obtained with different methods for estimating GABA turnover in rat neostriatum.Biochem. Pharmacol. 36,15391544.
  • 56
    Porter T.G. & Martin D.L. (1984) Evidence for feedback regulation of glutamate decarboxylase by γ-aminobutyric acid. J. Neurochem. 43,14641467.
  • 57
    Preece N.E. & Cerdan S. (1996) Metabolic precursors and compartmentation of cerebral GABA in vigabatrin-treated rats.J. Neurochem. 67,17181725.
  • 58
    Reubi J.C., Van den Berg C.J., Cuénod M. (1978) Glutamine as precursor for the GABA and glutamate transmitter pools.Neurosci. Lett. 10,171174.
  • 59
    Roberts E. (1991) Living systems are tonically inhibited, autonomous optimizers, and disinhibition coupled to variability generation is their major organizing principle : inhibitory command-control at levels of membrane, genome, metabolism, brain, and society.Neurochem. Res. 16,409421.
  • 60
    Roberts E. & Bregoff H.M. (1953) Transmination of γ-aminobutyric acid and β-alanine in brain and liver. J. Biol. Chem. 201,393398.
  • 61
    Roberts E. & Frankel S. (1950) γ-Aminobutyric acid in brain : its formation from glutamic acid. J. Biol. Chem. 187,5563.
  • 62
    Roepstorff A. & Lambert J.D. (1992) Comparison of the effect of the GABA uptake blockers, tiagabine and nipecotic acid, on inhibitory synaptic efficacy in hippocampal CA1 neurones.Neurosci. Lett. 146,131134.
  • 63
    Salganicoff L. & De Robertis E. (1965) Subcellular distribution of the enzymes of the glutamic acid, glutamine and γ-aminobutyric acid cycles in rat brain. J. Neurochem. 12,287309.
  • 64
    Schousboe A. (1990) Neurochemical alterations associated with epilepsy or seizure activity, inComprehensive Epileptology (Dam M. and Gram L., eds), pp. 116. Raven Press, New York.
  • 65
    Schousboe A. & Redburn D.A. (1995) Modulatory actions of gamma aminobutyric acid (GABA) on GABA type A receptor subunit expression and function.J. Neurosci. Res. 41,117.
  • 66
    Schousboe A., Wu J.Y., Roberts E. (1973) Purification and characterization of the 4-aminobutyrate-2,ketoglutarate transaminase from mouse brain.Biochemistry 12,28682873.
  • 67
    Schousboe A., Svenneby G., Hertz L. (1977) Uptake and metabolism of glutamate in astrocytes cultured from dissociated mouse brain hemispheres.J. Neurochem. 29,9991005.
  • 68
    Schousboe A., Larsson O.M., Hertz L., Krogsgaard-Larsen P. (1981) Heterocyclic GABA analogues as selective inhibitors of astroglial GABA uptake.Adv. Biochem. Psychopharmacol. 29,135141.
  • 69
    Schousboe A., Westergaard N., Sonnewald U., Petersen S.B., Huang R., Peng L., Hertz L. (1993) Glutamate and glutamine metabolism and compartmentation in astrocytes.Dev. Neurosci. 15,359366.
  • 70
    Schwarzer C. & Sperk G. (1995) Hippocampal granule cells express glutamic acid decarboxylase-67 after limbic seizures in the rat.Neuroscience 69,705709.DOI: 10.1016/0306-4522(95)00348-M
  • 71
    Seiler N. (1980) On the role of GABA in vertebrate polyamine metabolism.Physiol. Chem. Phys. 12,411429.
  • 72
    Shank R.P. & Campbell G.L. (1984) α-Ketoglutarate and malate uptake and metabolism by synaptosomes : further evidence for an astrocytes-to-neuron metabolic shuttle. J. Neurochem. 42,11531161.
  • 73
    Shank R.P. & Reife R.A. (1999) Agents for the treatment of epilepsy, inQuick Look : Pharmacology (Raffa R., ed), in press. Fence Creek Publishing, Lyndell, Pennsylvania.
  • 74
    Shank R.P., Bennett G.S., Freytag S.O., Campbell G.L. (1985) Pyruvate carboxylase : an astrocyte-specific enzyme implicated in the replenishment of amino acid neurotransmitter pools.Brain Res. 329,364367.
  • 75
    Shank R.P., Baldy W.J., Ash C.W. (1989) Glutamine and 2-oxoglutarate as metabolic precursors of the transmitter pools of glutamate and GABA : correlation of regional uptake by rat brain synaptosomes.Neurochem. Res. 4,371376.
  • 76
    Sheikh S.N. & Martin D.L. (1998) Elevation of brain GABA levels with vigabatrin (gamma-vinyl GABA) differentially affects GAD65 and GAD67 expression in various regions of rat brain.J. Neurosci. Res. 52,736741.
  • 77
    Sihra T.S. & Nicholls D.G. (1987) γ-Aminobutyrate can be released exocytotically from guinea-pig cerebral cortical synaptosomes. J. Neurochem. 49,261267.
  • 78
    Sloviter R.S., Dichter M.A., Rachinsky T.L., Dean E., Goodman J.H., Sollas A.L., Martin D.L. (1996) Basal expression and induction of glutamate decarboxylase and GABA in excitatory granule cells of the rat and monkey hippocampal dentate gyrus.J. Comp. Neurol. 373,593618.DOI: 10.1002/(SICI)1096-9861(19960930)373:4<593::AID-CNE8>3.3.CO;2-S
  • 79
    Sokoloff L., Reivich M., Kennedy C., DesRosiers M.H., Patlak C.S., Pettigrew K.D., Sakurada O., Shinobara M. (1977) The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization : theory, procedure, and normal values in the conscious and anesthetized albino rat. J. Neurochem. 28,897916.
  • 80
    Sonnewald U., Westergaard N., Hassel B., Muller T.B., Unsgard G., Fonnum F., Hertz L., Schousboe A., Petersen S.B. (1993 a) NMR spectroscopic studies of 13C acetate and 13C glucose metabolism in neocortical astrocytes : evidence for mitochondrial heterogeneity. Dev. Neurosci. 15,351358.
  • 81
    Sonnewald U., Westergaard N., Schousboe A., Svendsen J.S., Unsgård G., Petersen S.P. (1993 b) Direct demonstration by [13C]NMR spectroscopy that glutamine from astrocytes is a precursor for GABA synthesis in neurons. Neurochem. Int. 1,1929.
  • 82
    Sonnewald U., Hertz L., Schousboe A. (1998) Mitochondrial heterogeneity in the brain at the cellular level.J. Cereb. Blood Flow Metab. 18,231237.
  • 83
    Tapia R. (1975) Biochemical pharmacology in CNS, inHandbook of Psychopharmacology, Vol. 4 (Iversen L. L., Iversen S. D., and Snyder S. H., eds), pp. 158. Plenum Press, New York.
  • 84
    Waagepetersen H.S., Bakken I.J., Larsson O.M., Sonnewald U., Schousboe A. (1998 a) Metabolism of lactate in cultured GABAergic neurons studied by 13C-NMR spectroscopy. J. Cereb. Blood Flow Metab. 18,109117.
  • 85
    Waagepetersen H.S., Bakken I.J., Larsson O.M., Sonnewald U., Schousboe A. (1998 b) Comparison of lactate and glucose metabolism in cultured neocortical neurons and astrocytes using 13C NMR spectroscopy. Dev. Neurosci. 20,310320.
  • 86
    Waagepetersen H.S., Sonnewald U., Larsson O.M., Schousboe A. (1999 a) Synthesis of vesicular GABA from glutamine involves TCA cycle metabolism in neocortical neurons. J. Neurosci. Res. 57,342349.DOI: 10.1002/(SICI)1097-4547(19990801)57:3<342::AID-JNR6>3.3.CO;2-O
  • 87
    Waagepetersen H.S., Sonnewald U., Larsson O.M., Schousboe A. (1999 b) Compartmentation of TCA cycle metabolism in cultured neocortical neurons revealed by 13C MR spectroscopy. Neurochem. Int. (in press).
  • 88
    Westergaard N., Larsson O.M., Jensen B., Schousboe A. (1992) Synthesis and release of GABA in cerebral cortical neurons co-cultured with astrocytes from cerebral cortex or cerebellum.Neurochem. Int. 20,567575.
  • 89
    Westergaard N., Sonnewald U., Petersen S.B., Schousboe A. (1995 a) Glutamate and glutamine metabolism in cultured GABAergic neurons studied by 13C NMR spectroscopy may indicate compartmentation and mitochondrial heterogeneity. Neurosci. Lett. 185,2428.
  • 90
    Westergaard N., Sonnewald U., Schousboe A. (1995 b) Metabolic trafficking between neurons and astrocytes : the glutamate/glutamine cycle revisited. Dev. Neurosci. 17,203211.
  • 91
    Wolff J.R., Joo F., Dames W. (1978) Plasticity in dendrites shown by continuous GABA administration in superior cervical ganglion of adult rat.Nature 274,7274.
  • 92
    Wood J.D. & Kurylo E. (1980) Drug induced changes in the GABA content of nerve terminals determined using a synaptosomal model.Brain Res. Bull. 5,S925S927.
  • 93
    Wu J., Matsuda T., Roberts E. , (1973) Purification and characterization of glutamate decarboxylase from mouse brain.J. Biol. Chem. 248,30293034.
  • 94
    Yasumi M., Sato K., Shimada S., Nishimura M., Tohyama M. (1997) Regional distribution of GABA transporter 1 (GAT1) mRNA in the rat brain : comparison with glutamic acid decarboxylase67 (GAD67) mRNA localization. Brain Res. Mol. Brain Res. 44,205218.
  • 95
    Yu A.C.H., Drejer J., Hertz L., Schousboe A. (1983) Pyruvate carboxylase activity in primary cultures of astrocytes and neurons.J. Neurochem. 41,14841487.
  • 96
    Yu A.C.H., Fisher T.E., Hertz E., Tildon J.T., Schousboe A., Hertz L. (1984) Metabolic fate of [14C]-glutamine in mouse cerebral neurons in primary cultures. J. Neurosci. Res. 11,351357.
  • 97
    Yudkoff M., Zaleska M.M., Nissim I., Nelson D., Erecińska M. (1989) Neuronal glutamine utilization : pathways of nitrogen transfer studied with [15N]glutamine. J. Neurochem. 53,632640.