GABA signalling: therapeutic targets for epilepsy, Parkinson’s disease and Huntington’s disease

Bibliography

• SOLIMENA M, AGGUJARO D, MUNTZEL C et al.: Associa-tion of GAD-65, but not of GAD-67, with the Golgi complex of transfected Chinese hamster ovary cells mediated by the N-terminal region. Proc. Natl. Acad. Sci. USA (1993) 90:3073–3077.
   PubMed Web of Science ®Google Scholar
• KAUFMAN DL, HOUSER CR, TOBIN AJ: Two forms of the gamma-aminobutyric acid synthetic enzyme glutamate decarboxylase have distinct intraneuronal distributions and cofactor interactions. J. Neurochem. (1991) 56:720–723.
   PubMed Web of Science ®Google Scholar
• ERLANDER MG, TILLAKARATNE NJ, FELDBLUM S, PATELN,TOBIN AJ: Two genes encode distinct glutamate decarboxylases. Neuron (1991) 7:91–100.
   PubMed Web of Science ®Google Scholar
• MARTIN DL, MARTIN SB, WU SIESPINA N: 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. (1991) 11:2725–2731.
   PubMed Web of Science ®Google Scholar
• MCINTIRE SL, REIMER RJ, SCHUSKE K, EDWARDS RH, JORGENSEN EM: Identification and characterization of the vesicular GABA transporter. Nature (1997) 389:870–876.
   PubMed Web of Science ®Google Scholar
• MACDONALD RL, OLSEN RW: GABAA r ecep to r channels. Ann. Rev. Neurosci. (1994) 17:569–602.
   PubMed Web of Science ®Google Scholar
• WHITING PJ, MCKERNAN RM, WAFFORD KA: Structure and pharmacology of vertebrate GABAA receptor subtypes. Int. Rev. Neurobiol. (1995) 38:95–138.
   PubMed Web of Science ®Google Scholar
• WHITING PJ: The GABAA receptor gene family: new targets for therapeutic intervention. Neurochem. Int. (1999) 34:387–390.
   PubMed Web of Science ®Google Scholar
• •A short review of GABAA receptor subunit properties in journal issue dedicated to GABA.
   Google Scholar
• JONES KA, BOROWSKY B, TAMM JA et al.: GABA(B) receptors function as a heteromeric assembly of the subunits GABA(B)R1 and GABA(B)R2. Nature (1998) 396:674–679.
   PubMed Web of Science ®Google Scholar
• KAUPMANN K, HUGGEL K, HEID J: Expression cloningof GABAB receptors uncovers similarity to metabotropic glutamate receptors. Nature (1997) 386:239–246.
   PubMed Web of Science ®Google Scholar
• WHITE JH, WISE A, MAIN MJ et al.: Heterodimerization is required for the formation of a functional GABA(B) receptor. Nature (1998) 396:679–682.
   PubMed Web of Science ®Google Scholar
• KAUPMANN K, MALITSCHEK B, SCHULER V et al: GABA(B)-receptor subtypes assemble into functional heteromeric complexes. Nature (1998) 396:683–687.
   PubMed Web of Science ®Google Scholar
• GUASTELLA J, NELSON N, NELSON H et al.: Cloning and expression of a rat brain GABA transporter. Science (1990) 249:1303–1306.
   PubMed Web of Science ®Google Scholar
• BORDEN LA, DHAR TG, SMITH KE, BRANCHEK TA, GLUCHOWSKI C, WEINSHANK RL: Cloning of the human homologue of the GABA transporter GAT-3 and identi-fication of a novel inhibitor with selectivity for this site. Receptors Channels (1994) 2:207–213.
   PubMedGoogle Scholar
• MINELLI A, BRECHA NC, KARSCHIN C, DEBIASI S, CONTI F: GAT-1, a high-affinity GABA plasma membrane transporter, is localized to neurons and astroglia in the cerebral cortex. J. Neurosci. (1995) 15:7734–7746.
   PubMed Web of Science ®Google Scholar
• CONTI F, MELONE M, DE BIASI S, MINELLI A, BRECHA NC, DUCATI A: Neuronal and glial localization of GAT-1, a high-affinity gamma-aminobutyric acid plasma membrane transporter, in human cerebral cortex: with a note on its distribution in monkey cortex. J. Comp. Neurol. (1998) 396:51–63.
   PubMed Web of Science ®Google Scholar
• WORRALL DM, WILLIAMS DC: Sodium ion-dependent transporters for neurotransmitters: a review of recent developments. Biochem. J. (1994) 297:425–436.
   PubMed Web of Science ®Google Scholar
• AMARA SG, ARRIZA JL: Neurotransmitter transporters: three distinct gene families. Curr. Opin. Neurobiol. (1993) 3:337–344.
   PubMedGoogle Scholar
• MEDINA-KAUWE LK, TILLAKARATNE NJ, WU JY, TOBINAJ: A rat brain cDNA encodes enzymatically active GABA transaminase and provides a molecular probe for GABA-catabolizing cells. J. Neurochem. (1994) 62:1267–1275.
   PubMed Web of Science ®Google Scholar
• MA W, BEHAR T, MARIC D, MARIC I, BARKER JL:Neuroepithelial cells in the rat spinal cord express glutamate decarboxylase immunoreactivity in vivo and in vitro. J. Comp. Neurol (1992) 325:257–270.
   PubMed Web of Science ®Google Scholar
• BARKER JL, BEHAR T, LI YX et al: GABAergic cells andsignals in CNS development. Perspect. Dev. Neurobiol. (1998) 5:305–22.
   PubMedGoogle Scholar
• GREIF KF, TILLAKARATNE NJ, ERLANDER MG, FELDBLUMS, TOBIN AJ: Transient increase in expression of a glutamate decarboxylase (GAD) mRNA during the postnatal development of the rat striatum. Dev. (1992) 153:158–164.
   Google Scholar
• BOWERS G, CULLINAN WE, HERMAN JP: Region-specificregulation of glutamic acid decarboxylase (GAD) mRNA expression in central stress circuits. J Neurosci. (1998) 18:5938–47.
   PubMed Web of Science ®Google Scholar
• SLOVITER RS, DICHTER MA, RACHINSKY TL et al: Basalexpression and induction of glutamate decarboxylase and GABA in excitatory granule cells of the rat and monkey hippocampal dentate gyrus. J. Comp. Neurol. (1996) 373:593–618.
   PubMed Web of Science ®Google Scholar
• SEGOVIA J, TILLAKARATNE NJ, WHELAN K, TOBIN AJ,GALE K: Parallel increases in striatal glutamic acid decarboxylase activity and mRNA levels in rats with lesions of the nigrostriatal pathway. Brain Res. (1990) 529:345–348.
   PubMed Web of Science ®Google Scholar
• FELDBLUM S, ERLANDER MG, TOBIN AJ: Different distri-butions of GAD65 and GAD67 mRNAs suggest that the two glutamate decarboxylases play distinctive functional roles. J Neurosci. Res. (1993) 34:689–706.
   PubMed Web of Science ®Google Scholar
• DUMOULIN A, ALONSO G, PRIVAT A, FELDBLUM S: Biphasic response of spinal GABAergic neurons after a lumbar rhizotomy in the adult rat. Eur. J. Neurosci. (1996) 8:2553–2563.
   PubMed Web of Science ®Google Scholar
• DRENGLER SM, LORDEN JF, BILLITZ MS, OLTMANS GA:Adrenergic agents inhibit rapid increases in cerebellar Purkinje cell glutamic acid decarboxylase (GAD67) mRNA levels after climbing fiber lesions or reserpine treatment. J Neurosci. (1996) 16:1844–1851.
   PubMed Web of Science ®Google Scholar
• DELFS JM, CIARAMITARO VM, PARRY TJ, CHESSELET MF:Subthalamic nucleus lesions: widespread effects on changes in gene expression induced by nigrostriatal dopamine depletion in rats. J. Neurosci. (1995) 15:6562–6575.
   PubMed Web of Science ®Google Scholar
• MARTIN DL, BARKE KE: Are GAD65 and GAD67 associ-ated with specific pools of GABA in brain? Perspect. Dev. Neurobiol. (1998) 5:119–129.
   Google Scholar
• CHANG Y, WANG R, BAROT S, WEISS DS: Stoichiometryof a recombinant GABAA receptor. J Neurosci. (1996) 16:5415–5424.
   PubMed Web of Science ®Google Scholar
• TRETTER V, EHYA N, FUCHS K, SIEGHART W: Stoichio-metry and assembly of a recombinant GABAA receptor subtype. J. Neurosci. (1997) 17:2728–2737.
   PubMed Web of Science ®Google Scholar
• MCKERNAN RM, ROSAHL TVV, REYNOLDS DS et al: Sedative but not anxiolytic properties of benzodi-azepines are mediated by the GABA(A) receptor alpha1 subtype. Nat. Neurosci. (2000) 3:587–592.
   PubMed Web of Science ®Google Scholar
• ••The first demonstration that sedative and anxiolytic proper-ties of benzodiazepines are associated with separate GABAA receptor subtypes. This work will allow refinement of drug targeting to minimise side effects.
   Google Scholar
• CARLSON BX, ELSTER L, SCHOUSBOE A: Pharma-cological and functional implications of developmentally-regulated changes in GABA(A) receptor subunit expression in the cerebellum. Eur. Pharmacol (1998) 352:1–14.
   PubMed Web of Science ®Google Scholar
• BROOKS-KAYAL AR, SHUMATE MD, JIN H, RIKHTER TY, COULTER DA: Selective changes in single cell GABA(A) receptor subunit expression and function in temporal lobe epilepsy. Nature Med. (1998) 4:1166–1172.
   PubMed Web of Science ®Google Scholar
• BROOKS-KAYAL AR, JIN H, PRICE M,DICHTER MA: Developmental expression of GABA(A) receptor subunit mRNAs in individual hippocampal neurons in vitro and in vivo. J. Neurochem. (1998) 70:1017–1028.
   PubMed Web of Science ®Google Scholar
• MELDRUM B,CHAPMAN A: Epileptic seizures and epilepsy. In: Basic Neurochemistry: molecular, cellular and medical aspects. Siegel GJ et al. (Eds.), Lippincott-Raven Publishers, Philadelphia, PA (1999):755–768.
   Google Scholar
• ACSADY L, KAMONDI A, SIK A, FREUND T, BUZSAKI G: GABAergic cells are the major postsynaptic targets of mossy fibers in the rat hippocampus. j Neurosci. (1998) 18:3386–3403.
   PubMed Web of Science ®Google Scholar
• •A thorough anatomical study showing that mossy fibre synapses on GABAergic hippocampal cells are fundamen-tally different from synapses onto other cell types.
   Google Scholar
• FISHER PD, SPERBER EF, MOSHE SL: flippocampal sclerosis revisited. Brain Dev. (1998) 20:563–573.
   PubMed Web of Science ®Google Scholar
• BLUMCKE I, BECK H, LIE AA, WIESTLER OD: Molecular neuropathology of human mesial temporal lobe epilepsy. Epilepsy Res. (1999) 36:205–223.
   PubMed Web of Science ®Google Scholar
• ••A thorough review of hippocampal sclerosis.
   Google Scholar
• HOUSER CR: Morphological changes in the dentate gyrus in human temporal lobe epilepsy. Epilepsy Res. Suppl. (1992) 7:223–234.
   PubMedGoogle Scholar
• FRANCK JE, POKORNY J, KUNKEL DD, SCHWARTZKROIN PA: Physiologic and morphologic characteristics of granule cell circuitry in human epileptic hippocampus. Epilepsia (1995) 36:543–558.
   PubMed Web of Science ®Google Scholar
• PARENT JM, YU TW, LEIBOWITZ RT, GESCHWIND DH, SLOVITER RS, LOWENSTEIN DH: Dentate granule cell neurogenesis is increased by seizures and contributes to aberrant network reorganization in the adult rat hippocampus. Neurosci. (1997) 17:3727–3738.
   PubMed Web of Science ®Google Scholar
• MATHERN GW, MENDOZA D, LOZADA A et al.: Hippocampal GABA and glutamate transporter immunoreactivity in patients with temporal lobe epilepsy. Neurology (1999) 52:453–472.
   PubMed Web of Science ®Google Scholar
• HOOGLAND G, HENS pH, DE WIT M et al.: Glutamate and7-aminobutyric acid content and release of synapto-somes from temporal lobe epilepsy patients. J. Neurosci. Res. (2000) 60:686–695.
   Google 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) 26:245–254.
   PubMed Web of Science ®Google Scholar
• TILLAKARATNE NJ, MOURIA M, ZIV NB, ROY RR, EDGERTON VR, TOBIN AJ: Increased expression of glutamate decarboxylase (GAD67) in feline lumbar spinal cord after complete thoracic spinal cord transection. j Neurosci. Res. (2000) 60:219–230.
   PubMed Web of Science ®Google Scholar
• CONDIE BG, BAIN G, GOTTLIEB DI, CAPECCHI MR: Cleftpalate in mice with a targeted mutation in the 7-aminobutyric acid-producing enzyme glutamic acid decarboxylase 67. Proc. Natl. Acad. Sci. USA (1997) 94:11451–11455.
   PubMed Web of Science ®Google Scholar
• ASADA H, KAWAMURA Y, MARUYAMA K et al: Cleftpalate and decreased brain 7-aminobutyric acid in mice lacking the 67-kDa isoform of glutamic acid decarboxylase. Proc. NMI Acad. Sci. USA (1997) 94:6496–6499.
   PubMed Web of Science ®Google Scholar
• STORK O, JI F-Y, KANEKO K et al: Postnatal develop-ment of a GABA deficit and disturbance of neural functions in mice lacking GAD65. Brain Res. (2000) 865:45–58.
   PubMed Web of Science ®Google Scholar
• KASH SF, JOHNSON RS, TECOTT LH et al: Epilepsy inmice deficient in the 65-kDa isoform of glutamic acid decarboxylase. Proc. NMI Acad. Sci. USA (1997) 94:14060–14065.
   PubMed Web of Science ®Google Scholar
• HENSCH TK, FAGIOLINI M, MATAGA N, STRYKER MP, BAEKKESKOV S, KASH SF: local GABA circuit control of experience-dependent plasticity in developing visual cortex. Science (1998) 282:1504–1508.
   PubMed Web of Science ®Google Scholar
• TIAN N, PETERSEN C, KASH S, BAEKKESKOV S,COPENHAGEN D, NICOLL R: The role of the synthetic enzyme GAD65 in the control of 7-aminobutyric acid release. Proc. Natl. Acad. Sci. USA (1999) 96:12911–12916.
   PubMedGoogle Scholar
• GASPARY HL, WANG W, RICHERSON GB: Carrier-mediated GABA release activates GABA receptors on hippocampal neurons. J. Neurophysiol. (1998) 80:270–281.
   PubMed Web of Science ®Google Scholar
• ••The authors provide strong evidence that carrier-mediatedGABA release is sufficient to activate GABA receptors.
   Google Scholar
• SCHOFFELMEER AN, VANDERSCHUREN LJ, DE VRIES TJ, HOGENBOOM F, WARDEH G, MULDER AH: Synergisti-cally interacting dopamine Di and NMDA receptors mediate nonvesicular transporter-dependent GABA release from rat striatal medium spiny neurons. J Neurosci. (2000) 20:3496–3503.
   PubMed Web of Science ®Google Scholar
• ••NMDA receptor activation causes increased intracellular Na+thus increasing the probability of transporter-reversal. This study shows that Di DA receptor activation also triggers transporter reversal, though by a different mechanism. Thus, both receptor types can act together to stimulate transporter-mediated GABA release.
   Google Scholar
• BELHAGE B, HANSEN GH, SCHOUSBOE A: Depolariza-tion by 10- and glutamate activates different neurotransmitter release mechanisms in GABAergic neurons: vesicular versus non-vesicular release of GABA. Neurosci. (1993) 54:1019–1034.
   PubMed Web of Science ®Google Scholar
• DURING MJ, RYDER KM, SPENCER DD: Hippocampal GABA transporter function in temporal-lobe epilepsy. Nature (1995) 376:174–177.
   PubMed Web of Science ®Google Scholar
• ••Using both human and animal studies, the authors show thatGAT function is attenuated in epileptogenic hippocampus. The data suggest that GAT normally functions to alleviate seizure activity.
   Google Scholar
• LOUP F, WIESER H-G, YONEKAWA Y, AGUZZI A, FRITSCHY J-M: Selective alterations in GABAA receptor subtypes in human temporal lobe epilepsy./ Neurosci. (2000) 20:5401–5419.
   PubMed Web of Science ®Google Scholar
• •This immunohistochemical analysis of three receptor subtypes reveals a significant reorganisation of subtypes in TLE with sclerosis as compared to non-sclerotic TLE.
   Google Scholar
• HAND KS, BAIRD VH, VAN PAESSCHEN W et al.: Centralbenzodiazepine receptor autoradiography in hippocampal sclerosis. Br. J. Pharmacol. (1997) 122:358–364.
   Google Scholar
• KOEPP MJ, RICHARDSON MP, BROOKS DJ et al.: Cerebralbenzodiazepine receptors in hippocampal sclerosis. An objective in vivo analysis. Brain (1996) 119:1677–1687.
   Google Scholar
• ISOKAWA M: Decrement of GABAA receptor-mediatedinhibitory postsynaptic currents in dentate granule cells in epileptic hippocampus. j Neurophysiol. (1996) 75:1901–1908.
   PubMed Web of Science ®Google Scholar
• FRITSCHY JM, KIENER T, BOUILLERET V, LOUP F:GABAergic neurons and GABA(A)-receptors in temporal lobe epilepsy. Neurochem. Int. (1999) 34:435–445.
   PubMed Web of Science ®Google Scholar
• SLOVITER RS: The functional organization of the hippocampal dentate gyrus and its relevance to the pathogenesis of temporal lobe epilepsy. Ann. Neurol. (1994) 35:640–654.
   PubMed Web of Science ®Google Scholar
• SLOVITER RS: Permanently altered hippocampal structure, excitability and inhibition after experi-mental status epilepticus in the rat: the 'dormant basket cell' hypothesis and its possible relevance to temporal lobe epilepsy. Hippocampus (1991) 1:41–66.
   PubMedGoogle Scholar
• BABB TL, PRETORIUS JK, KUPFER WR, CRANDALL PH: Glutamate decarboxylase-immunoreactive neurons are preserved in human epileptic hippocampus. Neurosci. (1989) 9:2562–2574.
   PubMed Web of Science ®Google Scholar
• AVOLI M: GABA-mediated synchronous potentials and seizure generation. Epilepsia (1996) 37:1035–1042.
   PubMed Web of Science ®Google Scholar
• OLSEN RW, AVOLI M: GABA and epileptogenesis. Epilepsia (1997) 38:399–407.
   PubMed Web of Science ®Google Scholar
• •A review of GABA receptors and epileptogenesis based on presentations to an international symposium 'Focus on Epilepsy III: GABA and epileptogenesis'.
   Google Scholar
• PETERSON GM, RIBAK CE: flippocampus of the seizure- sensitive gerbil is a specific site for anatomical changes in the GABAergic system. J. Comp. Neurol. (1987) 261:405–422.
   PubMed Web of Science ®Google Scholar
• BUCKMASTER PS, JONGEN-RELO AL, DAVARI SB, WONG EH: Testing the disinhibition hypothesis of epilepto-genesis in vivo and during spontaneous seizures. J Neurosci. (2000) 20:6232–6240.
   PubMed Web of Science ®Google Scholar
• •The authors test the 'disinhibition hypothesis' with electro-physiological, immunohistochemical and in situ methods. They provide evidence that reduced inhibition occurs after, not before seizure activity.
   Google Scholar
• LOSCHER W: Valproate: a reappraisal of its pharmaco-dynamic properties and mechanisms of action. Prog. Neurobiol (1999) 58:31–59.
   PubMed Web of Science ®Google Scholar
• GOLDLUST A, SU T-Z, WELTY DF, TAYLOR CP, OXENDERDL: Effects of anticonvulsant drug gabapentin on the enzymes in metabolic pathways of glutamate and GABA. Epilepsy Res. (1995) 22:1–11.
   PubMed Web of Science ®Google Scholar
• DEGIORGIO CM, SCHACHTER SC, HANDFORTH A et al.:Prospective long-term study of vag-us nerve stimula-tion for the treatment of refractory seizures. Epilepsia (2000) 41:1195–1200.
   PubMed Web of Science ®Google Scholar
• HANDFORTH A, DEGIORGIO CM, SCHACHTER SC et al.:Vag-us nerve stimulation therapy for partial-onset seizures: a randomized active-control trial. Neurology (1998) 51:48–55.
   PubMed Web of Science ®Google Scholar
• BEHRSTOCK SP, ANANTHARAM V, THOMPSON KW, SCHWEITZER ES, TOBIN AJ: Conditionally-immortalized astrocytic cell line expresses GAD and secretes GABA under tetracycline regulation. J. Neurosci. Res. (2000) 60:302–310.
   PubMed Web of Science ®Google Scholar
• LOSCHER W, EBERT U, LEHMANN H, ROSENTHAL C, NIKKAH G: Seizure suppression in kindling epilepsy by grafts of fetal GABAergic neurons in rat substantia nigra. j Neurosci. Res. (1998) 51:196–209.
   PubMed Web of Science ®Google Scholar
• THOMPSON K, ANANTHARAM V, BEHRSTOCK S, BONGARZONE E, CAMPAGNONI A, TOBIN AJ: Conditionally immortalized cell lines, engineered to produce and release GABA, modulate the development of behavioral seizures. Exp. Neurol. (2000) 161 :481–489.
   PubMed Web of Science ®Google Scholar
• BJORKLUND A, LINDVALL O: Cell replacementtherapies for central nervous system disorders. Nat. Neurosci. (2000) 3:537–544.
   PubMed Web of Science ®Google Scholar
• SHETTY AK, TURNER DA: Fetal hippocampal graftscontaining CA3 cells restore host hippocampal glutamate decarboxylase-positive interneuron numbers in a rat model of temporal lobe epilepsy. J Neurosci. (2000) 20:8788–8801.
   PubMed Web of Science ®Google Scholar
• •This immunohistochemical study shows that CA3 hippocampal cells possess properties that influence GAD expression in damaged hippocampus. Although there is no functional data, this study suggests that the CA3-mediated GAD expression may be important for seizure suppression.
   Google Scholar
• GALE K: Progression and generalization of seizuredischarge: anatomical and neurochemical substrates. Epilepsia (1988) 29:S15–S34.
   Web of Science ®Google Scholar
• IADAROLA MJ, GALE K: Substantianigra: site of anticon-vulsant activity mediated by gamma-aminobutyric acid. Science (1982) 218:1237–1240.
   PubMed Web of Science ®Google Scholar
• ••The authors demonstrate that GABA agonists injected intothe substantia nigra protect against seizures. This and subsequent work suggests that the substantia nigra could be a useful site for seizure treatment as it is remote from the highly excitable seizure focus.
   Google Scholar
• GALE K, IADAROLA MJ: Seizure protection andincreased nerve-terminal GABA: delayed effects of GABA transaminase inhibition. Science (1980) 208:288–291.
   PubMed Web of Science ®Google Scholar
• SHEHAB S, SIMKINS M, DEAN P, REDGRAVE P: Regionaldistribution of the anticonvulsant and behavioural effects of muscimol injected into the substantia nigra of rats. Eur.j Neurosci. (1996) 8:749–757.
   PubMed Web of Science ®Google Scholar
• MOSHE S, GARANT DS, SPERBER EF, VELISKOVA J, KUBOVA H, BROWN LL: Ontogeny and topography of seizure regulation by the substantia nigra. Brain & Devel (1995) 17:51–72.
   Web of Science ®Google Scholar
• TIMMERMAN W, WESTERINK BH: Brain microdialysis of GABA and glutamate: what does it signify? Synapse (1997) 27:242–261.
   PubMed Web of Science ®Google Scholar
• ••The authors compare a vast number of microdialysis studiesand conclude that GABA and glutamate are compartmental-ised. They contend that measurements outside of the synapse do not reflect true neurotransmission activity and that new approaches will be necessary to address the shortcomings of microdialysis.
   Google Scholar
• WU Y, PEARL SM, ZIGMOND MJ, MICHAEL AC: Inhibitoryglutamatergic regulation of evoked dopamine release in striatum. Neurosci. (2000) 96:65–72.
   PubMed Web of Science ®Google Scholar
• KULAGINA NV, SHANKAR L, MICHAEL AC: Monitoringglutamate and ascorbate in the extracellular space of brain tissue with electrochemical microsensors. Anal. Chem. (1999) 71:5093–5100.
   PubMed Web of Science ®Google Scholar
• •The authors describe the detection of glutamate in vivo with a microsensor. The authors suggest that the small size of their microsensor minimises tissue damage and therefore provides more reliable readings.
   Google Scholar
• ELLERBY LM, NISHIDA CR, NISHIDA F et al.: Encapsula- tion of proteins in transparent porous silicate glasses prepared by the sol-gel method. Science (1992) 255:1113–1115.
   PubMed Web of Science ®Google Scholar
• ••The first demonstration of bio-active molecule encapsula-tion in silicate. The sol-gel method described uses low temperatures and monitors pH in order to maintain enzymatic activity of encapsulated proteins.
   Google Scholar
• LAN EH, DUNN B: Encapsulation of the ferritin proteinin sol-gel derived silica glasses. j Sol-Gel Sci. Tech. (1996) 7:109–116.
   Web of Science ®Google Scholar
• MATTHEWS CC, ZIELKE HR, WOLLACK JB, FISHMAN PS:Enzymatic degradation protects neurons from glutamate excitotoxicity. J. Neurochem. (2000) 75:1045–1052.
   PubMed Web of Science ®Google Scholar
• KITADA T, ASAKAWA S, HATTORI N et al.: Mutations inthe parkin gene cause autosomal recessive juvenile parkinsonism. Nature (1998) 392:605–608.
   PubMed Web of Science ®Google Scholar
• NUSSBAUM RL, POLYMEROPOULOS MH: Genetics of Parkinson's disease. Hum. Mol. Genet. (1997) 6:1687–1691.
   PubMed Web of Science ®Google Scholar
• POLYMEROPOHLOS MH, LAVEDAN C, LEROY E et al.:Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science (1997) 276:2045–2047.
   PubMed Web of Science ®Google Scholar
• VILA M, HERRERO MT, LEVY R et al: Consequences of nigrostriatal denervation on the gamma-aminobutyric acidic neurons of substantia nigra pars reticulata and superior colliculus in parkinsonian syndromes. Neurology (1996) 46:802–809.
   PubMed Web of Science ®Google Scholar
• LEVY R, HERRERO MT, RUBERG M et al: Effects of nigros-triatal den ervation and L-dop a therapy on the GABAergic neurons in the striatum in MPTP-treated monkeys and Parkinson's disease: an in situ hybridi-zation study of GAD67 mRNA. Eur. J. Neurosci. (1995) 7:1199–1209.
   PubMedGoogle Scholar
• LAPRADE N, SOGHOMONIAN JJ: Gene expression of theGAD67 and GAD65 isoforms of glutamate decarboxy-lase is differentially altered in subpopulations of striatal neurons in adult rats lesioned with 6-0HDA as neonates. Synapse (1999) 33:36–48.
   PubMed Web of Science ®Google Scholar
• •These in situ hybridisation studies show that GAD expres-sion is regulated differently in neurones that project to the GPe than in those that project to the output nuclei.
   Google Scholar
• VERNIER P, JULIEN JF, RATABOUL P, FOURRIER O,FEUERSTEIN C, MALLET J: Similar time course changes in striatal levels of glutamic acid decarboxylase and proenkephalin mRNA following dopaminergic deaffer en tation in the rat. J. Neurochem. (1988) 51:1375–1380.
   PubMed Web of Science ®Google Scholar
• SOGHOMONIAN JJ, LAPRADE N: Glutamate decarboxy-lase (GAD67 and GAD65) gene expression is increased in a subpopulation of neurons in the putamen of Parkinsonian monkeys. Synapse (1997) 27:122–132.
   PubMed Web of Science ®Google Scholar
• KINCAID AE, ALBIN RL, NEWMAN SW, PENNEY JB, YOUNG AB: 6-hydroxydop amine lesions of the nigros-triatal pathway alter the expression of glutamate decarboxylase messenger RNA in rat globus pallidus projection neurons. Neurosci. (1992) 51 :705–718.
   PubMed Web of Science ®Google Scholar
• NISHINO N, FUJIWARA H, NOGUCHI-KUNO SA, TANAKA C: GABAAreceptor but not muscarinic receptor density was decreased in the brain of patients with Parkin-son's disease. Jpn. j Pharmacol (1988) 48:331–339.
   PubMedGoogle Scholar
• GERLACH M, GSELL W, KORNHUBER J et al.: A post mortem study on neurochemical markers of dopamin-ergic, GABA-ergic and glutamatergic neurons in basal ganglia-th alamo cortical circuits in Parkinson syndrome. Brain Res. (1996) 741:142–152.
   PubMed Web of Science ®Google Scholar
• KISH SJ, RAJPUT A, GILBERT J et al: Elevated gamma-aminobutyric acid level in striatal but not extrastriatal brain regions in Parkinson's disease: correlation with striatal dopamine loss. Ann. Neurol. (1986) 20:26–31.
   PubMed Web of Science ®Google Scholar
• ABARCA J, BUSTOS G: Differential regulation of glutamate, aspartate and y-aminobutyrate release by N-methyl-D-aspartate receptors in rat striatum after partial and extensive lesions to the nigro-striatal dopamine pathway. Neurochem. Int. (1999) 35:19–33.
   PubMed Web of Science ®Google Scholar
• ROBERTSON RG, GRAHAM WC, SAMBROOK MA, CROSSMAN AR: Further investigations into the pathophysiology of MPTP-induced parkinsonism in the primate: an intracerebral microdialysis study of gamma-aminobutyric acid in the lateral segment of the globus pallidus. Brain Res. (1991) 563:278–280.
   PubMed Web of Science ®Google Scholar
• LLOYD GK, LOWENTHAL A, JAVOY-AGID F, CONSTAN-TIDINIS J: GABAA receptor complex function in frontal cortex membranes from control and neurological patients. Eur.J. Pharmacol. (1991) 197:33–39.
   PubMed Web of Science ®Google Scholar
• GRIFFITHS PD, SAMBROOK MA, PERRY R, CROSSMAN AR: Changes in benzodiazepine and acetylcholine receptors in the globus pallidus in Parkinson's disease. J. Neurol ScL (1990) 100:131–136.
   PubMed Web of Science ®Google Scholar
• CHADHA A, DAWSON LG, JENNER PG, DUTY S: Effect of unilateral 6-hydroxydopamine lesions of the nigros-triatal pathway on GABAA receptor subunit gene expression in the rodent basal ganglia and thalamus. Neuroscience (1999) 95:119–126.
   Web of Science ®Google Scholar
• WALDVOGEL HJ, KUBOTA Y, FRITSCHY J, MOHLER H, FAULL RL: Regional and cellular localisation of GABA(A) receptor subunits in the human basal ganglia: An autoradiographic and immunohisto-chemical study. J. Comp. Neurol (1999) 415:313–340.
   PubMed Web of Science ®Google Scholar
• HARIZ MI, DE SALLES AA: The side-effects and complica-tions of posteroventr al pallidotomy. Acta Neurochir. Suppl. (Wien) (1997) 68:42–48.
   Google Scholar
• BRONSTEIN JM, DESALLES A, DELONG MR: Stereotactic pallidotomy in the treatment of Parkinson's disease. Arch. Neurol (1999) 56:1064–1069.
   PubMedGoogle Scholar
• DOSTROVSKY JO, LEVY R, WU JP, HUTCHISON WD, TASKER RR, LOZANO AM: Microstimulation-induced inhibition of neuronal firing in human globus pallidus. j Neurophysiol. (2000) 84:570–574.
   PubMed Web of Science ®Google Scholar
• ••Direct electrophysiological evidence that microstimulationinduces GABAergic inhibition in the GPi.
   Google Scholar
• HOUETO JL, DAMIER P, BEJJANI PB et al.: Subthalamic stimulation in Parkinson's disease: a multidisciplinary approach. Arch. Neurol. (2000) 57:461–465.
   PubMed Web of Science ®Google Scholar
• SELLAL F, HIRSCH E, LISOVOSKI F, MUTSCHLER V, COLLARD M, MARESCAUX C: Contralateral disappear-ance of parkinsonian signs after subthalamic hematoma. Neurology (1992) 42:255–156.
   PubMed Web of Science ®Google Scholar
• ALEXI T, BORLONGAN CV, FAULL RLM et al.: Neuropro-tective strategies for basal ganglia degeneration: Parkinson's and Huntington's diseases. Prog. Neurobiol. (2000) 60:409–470.
   PubMed Web of Science ®Google Scholar
• ••Informative review of current strategies for treating PD andHD, including transplantation, neuroprotection and growth factor treatment.
   Google Scholar
• OLANOW CW, KORDOWER JH, FREEMAN TB: Fetal nigral transplantation as a therapy for Parkinson's disease. TINS (1996) 19:102–109.
   PubMed Web of Science ®Google Scholar
• LINDVALL O: Cerebral implantation in movement disorders: state of the art. Mov. Disord. (1999) 14:201–205.
   PubMed Web of Science ®Google Scholar
• THE HUNTINGTON&S DISEASE COLLABORATIVE RESEARCH GROUP: A novel gene encoding a trinucleo-tide repeat that is expanded and unstable on Hunting-ton's disease chromosomes. Cell (1993) 72:971–983.
   Google Scholar
• REYNOLDS GP, PEARSON SJ: Brain GABA levels in asymptomatic Huntington's disease. N Engl. J Med. (1990) 323:682.
   PubMed Web of Science ®Google Scholar
• PEARSON SJ, REYNOLDS GP: Neocortical neurotrans-mitter markers in Huntington's disease. J. Neural Transm. Gen. Sect. (1994) 98:197–207.
   PubMedGoogle Scholar
• ALBIN RL, REINER A, ANDERSON KD, PENNEY JB, YOUNG AB: Striatal and nigral neuron subpopulations in rigid Huntington's disease: implications for the functional anatomy of chorea and rigidity-akinesia. Ann. Neurol. (1990) 27:357–365.
   PubMed Web of Science ®Google Scholar
• GLASS M, DRAGUNOW M, FAULL RLM: The pattern of neurodegeneration in Huntington's disease: a comparative study of cannabinoid, dopamine, adenosine and GABAA receptor alterations in the human basal ganglia in Huntington's disease. Neurosci-ence (2000) 97:505–519.
   PubMed Web of Science ®Google Scholar
• ••This receptor binding study correlates the progressive lossof receptor types with neurodegeneration. The data provide intriguing evidence that nerve terminal dysfunction occurs prior to cell loss.
   Google Scholar
• ALBIN RL, QIN Y, YOUNG AB, PENNEY JB, CHESSELET MF: Preproenkephalin messenger RNA-containing neurons in striatum of patients with symptomatic and presymptomatic Huntington's disease: an in situ hybridization study. Ann. Neurol. (1991) 30:542–549.
   PubMed Web of Science ®Google Scholar
• ALBIN RL, REINER A, ANDERSON KD et al.: Preferential loss of striato-external pallidal projection neurons in presymptomatic Huntington's disease. Ann. Neurol. (1992) 31:425–430.
   PubMed Web of Science ®Google Scholar
• AUGOOD SJ, FAULL RL, LOVE DR, EMSON PC: Reduction in enkephalin and substance P messenger RNA in the striatum of early grade Huntington's disease: a detailed cellular in situ hybridization study. Neurosci. (1996) 72:1023–1036.
   PubMed Web of Science ®Google Scholar
• REINER A, ALBIN RL, ANDERSON KD, D'AMATO CJ, PENNEY JB, YOUNG AB: Differential loss of striatal projection neurons in Huntington's disease. Proc. Natl. Acad. ScL USA (1988) 85:5733–5737.
   PubMed Web of Science ®Google Scholar
• FAULL RL, WALDVOGEL HJ, NICHOLSON LF, SYNEK BJ: The distribution of GABAA-benzodiazepine receptors in the basal ganglia in Huntington's disease and in the quinolinic acid-lesioned rat. Prog. Brain Res. (1993) 99:105–123.
   PubMed Web of Science ®Google Scholar
• KUNIG G, LEENDERS KL, SANCHEZ-PERNAUTE R et al.: Benzodiazepine receptor binding in Huntington's disease: [11C]flumazenil uptake measured using positron emission tomography. Ann. Neurol (2000) 47:644–648.
   PubMed Web of Science ®Google Scholar
• BRICKELL KL, NICHOLSON LFB, WALDVOGEL HJ, FAULL RLM: Chemical and anatomical changes in the striatum and substantia nigra following quinolinic acid lesions in the striatum of the rat: a detailed time course of the cellular and GABAA receptor changes. J. Chem. Neuroanal (1999) 17:75–97.
   PubMed Web of Science ®Google Scholar
• BACHOUD-LEVI A, REMY P, NGUYEN JP et al: Motor and cognitive improvements in patients with Huntington's disease after neural transplantation. Lancet (2000) 356:1975.
   PubMed Web of Science ®Google Scholar
• FINK JS, SCHUMACHER JM, ELLIAS SL et al.: Porcine xenografts in Parkinson's disease and Huntington's disease patients: preliminary results. Cell Transplant. (2000) 9:273–278.
   PubMed Web of Science ®Google Scholar
• WICHMANN T, DELONG MR: Path ophysiology of Parkinsonian motor abnormalities. Adv. Neurol. (1993) 60:53–61.
   PubMedGoogle Scholar