Extracellular level of GABA and Glu: in vivo microdialysis-HPLC measurements.

In spite of several studies showing specific physiological functions of changes in the extracellular level of the major excitatory and inhibitory transmitters, Glu and GABA within the brain ([Glu](EXT), [GABA](EXT)) the exact origin (neuronal vs. astroglial, synaptic vs. extrasynaptic) of Glu and GABA present in dialysate samples is still a matter of debate. For better understanding the significance of in vivo microdialysis data, here we discuss methodological details and problems in addition to regulation of [Glu](EXT) and [GABA](EXT). Changes in [Glu](EXT) and [GABA](EXT) under pathological conditions such as ischemia and epilepsy are also reviewed. Based on recent in vivo microdialysis data we argue that ambient [Glu](EXT) and [GABA](EXT)may have a functional role. It is suggested that specific changes in concentrations of Glu and GABA in dialysate samples together with their alterations independent of neuronal activity indicate the involvement of Glu and GABA in the information processing of the brain as essential signaling molecules of nonsynaptic transmission as well. Since various drugs are able to interfere with extrasynaptic signals in vivo, studying the extracellular cell-to-cell communication of brain cells represents a new aspect to improve drugs modulating Gluergic as well as GABAergic neurotransmission.

[1]  Lawrence K Duffy,et al.  An ultrastructural analysis of tissue surrounding a microdialysis probe , 1999, Journal of Neuroscience Methods.

[2]  T. Jay,et al.  Excitotoxicity in neurological disorders — the glutamate paradox , 2000, International Journal of Developmental Neuroscience.

[3]  Peter Lindroth,et al.  High performance liquid chromatographic determination of subpicomole amounts of amino acids by precolumn fluorescence derivatization with o-phthaldialdehyde , 1979 .

[4]  G. Juhász,et al.  Local perfusion of the thalamus with GABA increases sleep and induces long-lasting inhibition of somatosensory event-related potentials in cats , 1989, Neuroscience Letters.

[5]  F. Vajda.  Neuroprotection and neurodegenerative disease , 2002, Journal of Clinical Neuroscience.

[6]  T. Freund,et al.  Uridine release during aminopyridine-induced epilepsy , 2004, Neurobiology of Disease.

[7]  G. Sierra-Paredes,et al.  Effect of ionotropic glutamate receptors antagonists on the modifications in extracellular glutamate and aspartate levels during picrotoxin seizures: a microdialysis study in freely moving rats , 2000, Neurochemistry International.

[8]  N. O. Dalby.  GABA-level increasing and anticonvulsant effects of three different GABA uptake inhibitors , 2000, Neuropharmacology.

[9]  F. Mora,et al.  Effects of Endogenous Glutamate on Extracellular Concentrations of GABA, Dopamine, and Dopamine Metabolites in the Prefrontal Cortex of the Freely Moving Rat: Involvement of NMDA and AMPA/KA Receptors , 1999, Neurochemical Research.

[10]  Leif Hertz,et al.  Astrocytic control of glutamatergic activity: astrocytes as stars of the show , 2004, Trends in Neurosciences.

[11]  G. Juhász,et al.  In vivo blockade of thalamic GABA(B) receptors increases excitatory amino-acid levels. , 1996, European journal of pharmacology.

[12]  G. Juhász,et al.  Role of intracellular Ca2+ stores shaping normal activity in brain , 1999, Journal of neuroscience research.

[13]  F. Peña,et al.  Relationships Among Seizures, Extracellular Amino Acid Changes, and Neurodegeneration Induced by 4‐Aminopyridine in Rat Hippocampus: A Microdialysis and Electroencephalographic Study , 1999, Journal of neurochemistry.

[14]  D. D. Fraser,et al.  Astrocytic GABA receptors , 1994, Glia.

[15]  K. H. Backus,et al.  Glutamate opens Na+/K+ channels in cultured astrocytes , 1988, Glia.

[16]  Massimo Scanziani,et al.  Competing on the edge , 2002, Trends in Neurosciences.

[17]  G. Juhász,et al.  Uridine is released by depolarization and inhibits unit activity in the rat hippocampus. , 1999, Neuroreport.

[18]  M. Raiteri,et al.  Coexistence and function of different neurotransmitter transporters in the plasma membrane of CNS neurons , 2002, Progress in Neurobiology.

[19]  F. G. Diaz,et al.  Real-time measurement of ischemia-evoked glutamate release in the cerebral cortex of four and eleven vessel rat occlusion models , 1998, Brain Research.

[20]  Neurotoxicity of Lindane and Picrotoxin: Neurochemical and Electrophysiological Correlates in the Rat Hippocampus In Vivo , 2002, Neurochemical Research.

[21]  D. Kullmann.  Spillover and synaptic cross talk mediated by glutamate and GABA in the mammalian brain. , 2000, Progress in brain research.

[22]  R. Simon,et al.  The role of excitatory neurotransmitters in seizure-induced neuronal injury in rats , 1996, Brain Research.

[23]  Fang Liu,et al.  Glutamate-mediated astrocyte–neuron signalling , 1994, Nature.

[24]  G. Juhász,et al.  Slow wave sleep is accompanied by release of certain amino acids in the thalamus of cats , 1997, Neuroreport.

[25]  E. Pungor,et al.  Local depletion of monoamines induced with in vivo voltammetry in the cat brain , 1991, Neuroscience.

[26]  Janos P. Kiss,et al.  Nonsynaptic communication in the central nervous system , 2004, Neurochemistry International.

[27]  M. Suaud-Chagny,et al.  Microdialysis Monitoring of Catecholamines and Excitatory Amino Acids in the Rat and Mouse Brain: Recent Developments Based on Capillary Electrophoresis with Laser-Induced Fluorescence Detection—A Mini-Review , 2003, Cellular and Molecular Neurobiology.

[28]  K. Kekesi,et al.  Differential effects of nipecotic acid and 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridin-3-ol on extracellular gamma-aminobutyrate levels in rat thalamus. , 1997, European journal of pharmacology.

[29]  G. Juhász,et al.  Electrochemical calibration of in vivo brain dialysis samplers , 1989, Journal of Neuroscience Methods.

[30]  B. Westerink,et al.  Brain microdialysis of GABA and glutamate: What does it signify? , 1997, Synapse.

[31]  A. Schousboe,et al.  Role of astrocytic transport processes in glutamatergic and GABAergic neurotransmission , 2004, Neurochemistry International.

[32]  F. Mora,et al.  NMDA and AMPA/kainate glutamatergic agonists increase the extracellular concentrations of GABA in the prefrontal cortex of the freely moving rat: modulation by endogenous dopamine , 2002, Brain Research Bulletin.

[33]  Arne Schousboe,et al.  GABA transporters as drug targets for modulation of GABAergic activity. , 2004, Biochemical pharmacology.

[34]  G. Juhász,et al.  Sleep promoting effect of a putative glial gamma-aminobutyric acid uptake blocker applied in the thalamus of cats. , 1991, European journal of pharmacology.

[35]  F. Mora,et al.  Endogenous dopamine potentiates the effects of glutamate on extracellular GABA in the prefrontal cortex of the freely moving rat , 2000, Brain Research Bulletin.

[36]  D. Schoepp,et al.  Regulation of Neurotransmitter Release by Metabotropic Glutamate Receptors , 2000, Journal of neurochemistry.

[37]  H. Benveniste,et al.  Elevation of the Extracellular Concentrations of Glutamate and Aspartate in Rat Hippocampus During Transient Cerebral Ischemia Monitored by Intracerebral Microdialysis , 1984, Journal of neurochemistry.

[38]  I. Fried,et al.  Comparison of seizure related amino acid release in human epileptic hippocampus versus a chronic, kainate rat model of hippocampal epilepsy , 1996, Epilepsy Research.

[39]  J. Phillis,et al.  Characterization of modes of release of amino acids in the ischemic/reperfused rat cerebral cortex , 2003, Neurochemistry International.

[40]  Giorgio Carmignoto,et al.  Reciprocal communication systems between astrocytes and neurones , 2000, Progress in Neurobiology.

[41]  P. Kalivas,et al.  Regulation of Extracellular Glutamate in the Prefrontal Cortex: Focus on the Cystine Glutamate Exchanger and Group I Metabotropic Glutamate Receptors , 2005, Journal of Pharmacology and Experimental Therapeutics.

[42]  D. A. Brown,et al.  Distribution of gaba-receptors and gaba-carriers in the mammalian nervous system. , 1979, Journal de physiologie.

[43]  J. Watkins,et al.  Excitatory amino acid receptors and synaptic excitation in the mammalian central nervous system. , 1979, Journal de physiologie.

[44]  G. Juhász,et al.  GABAB receptor antagonist CGP-36742 enhances somatostatin release in the rat hippocampus in vivo and in vitro , 2003 .

[45]  H. Benveniste,et al.  Cellular reactions to implantation of a microdialysis tube in the rat hippocampus , 2004, Acta Neuropathologica.

[46]  J. Urenjak,et al.  Evidence Disputing the Link Between Seizure Activity and High Extracellular Glutamate , 1996, Journal of neurochemistry.

[47]  Y. Michotte,et al.  Effects of diazepam on extracellular brain neurotransmitters in pilocarpine-induced seizures in rats. , 1999, European journal of pharmacology.

[48]  G. Juhász,et al.  Effect of CGP 36742 on the extracellular level of neurotransmitter amino acids in the thalamus , 1999, Neurochemistry International.

[49]  E. Pehek,et al.  Sampling glutamate and GABA with microdialysis: suggestions on how to get the dialysis membrane closer to the synapse , 2004, Journal of Neuroscience Methods.

[50]  Arne Schousboe,et al.  Correlation between Anticonvulsant Activity and Inhibitory Action on Glial γ-Aminobutyric Acid Uptake of the Highly Selective Mouse γ-Aminobutyric Acid Transporter 1 Inhibitor 3-Hydroxy-4-amino-4,5,6,7-tetrahydro-1,2-benzisoxazole and ItsN-Alkylated Analogs , 2002, Journal of Pharmacology and Experimental Therapeutics.

[51]  G. Richerson,et al.  Role of the GABA transporter in epilepsy. , 2004, Advances in experimental medicine and biology.

[52]  K. Kekesi,et al.  Persistent depolarization and Glu uptake inhibition operate distinct osmoregulatory mechanisms in the mammalian brain , 2000, Neurochemistry International.

[53]  Y. Michotte,et al.  NMDA receptor‐mediated pilocarpine‐induced seizures: characterization in freely moving rats by microdialysis , 1997, British journal of pharmacology.

[54]  H. Bradford.  Glutamate, GABA and epilepsy , 1995, Progress in Neurobiology.

[55]  S. Bannai.  Exchange of cystine and glutamate across plasma membrane of human fibroblasts. , 1986, The Journal of biological chemistry.

[56]  M. Szente,et al.  Seizure, neurotransmitter release, and gene expression are closely related in the striatum of 4-aminopyridine-treated rats , 2003, Epilepsy Research.

[57]  G. Holmes,et al.  Seizure‐induced glutamate release in mature and immature animals: an in vivo microdialysis study , 1997, Neuroreport.

[58]  B. Westerink,et al.  HPLC conditions are critical for the detection of GABA by microdialysis , 2005, Journal of neurochemistry.

[59]  John D. Salamone,et al.  The GABA uptake inhibitor β-alanine reduces pilocarpine-induced tremor and increases extracellular GABA in substantia nigra pars reticulata as measured by microdialysis , 2004, Journal of Neuroscience Methods.

[60]  L. Massieu,et al.  Accumulation of Extracellular Glutamate by Inhibition of Its Uptake Is Not Sufficient for Inducing Neuronal Damage: An In Vivo Microdialysis Study , 1995, Journal of neurochemistry.

[61]  F. Mora,et al.  Changes in dialysate concentrations of glutamate and GABA in the brain: an index of volume transmission mediated actions? , 2003, Journal of neurochemistry.

[62]  Zheng-Xiong Xi,et al.  Group II metabotropic glutamate receptors modulate extracellular glutamate in the nucleus accumbens. , 2002, The Journal of pharmacology and experimental therapeutics.

[63]  Zheng-Xiong Xi,et al.  The Origin and Neuronal Function of In Vivo Nonsynaptic Glutamate , 2002, The Journal of Neuroscience.