Of mice, rats and men: Revisiting the quinolinic acid hypothesis of Huntington's disease

Progress in Neurobiology

Volumn 90, Issue 2, 2010, Pages 230-245

  Schwarcz, Robert ^a   Guidetti, Paolo ^a   Sathyasaikumar, Korrapati V ^a   Muchowski, Paul J ^b  

^a UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

3 Hydroxykynurenine; Excitotoxicity; Kynurenines; Microglia; Neuroprotection

Indexed keywords

2 AMINO 5 PHOSPHONOVALERIC ACID; 2 AMINO 7 PHOSPHONOHEPTANOIC ACID; 3 HYDROXYKYNURENINE; AMINO ACID DERIVATIVE; DEXTRO 2 AMINOADIPIC ACID; GLUTAMATE RECEPTOR; GLUTAMIC ACID; HUNTINGTIN; IBOTENIC ACID; KYNURENINE; KYNURENINE 3 MONOOXYGENASE; N METHYL DEXTRO ASPARTIC ACID RECEPTOR BLOCKING AGENT; NEUROTOXIN; POLYGLUTAMINE; QUINOLINIC ACID; TRYPTOPHAN;

BRAIN ISCHEMIA; CELL TRANSPLANTATION; CYTOTOXICITY; DEGENERATIVE DISEASE; DISEASE COURSE; DOPAMINERGIC NERVE CELL; DOPAMINERGIC SYSTEM; DRUG EFFICACY; DRUG RESEARCH; DRUG TARGETING; ENZYME INHIBITION; EXCITOTOXICITY; GENETIC MODEL; HUMAN; HUNTINGTON CHOREA; METABOLITE; MOLECULAR CLONING; NERVE CELL NECROSIS; NEUROCHEMISTRY; NEUROPROTECTION; NEUROTOXICITY; NONHUMAN; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN TARGETING; REVIEW; TOXICOKINETICS; YEAST;

ANIMALS; DISEASE MODELS, ANIMAL; DOPAMINE; HUMANS; HUNTINGTON DISEASE; KYNURENINE; MICE; MUTATION; PEPTIDES; QUINOLINIC ACID; RATS; RECEPTORS, GLUTAMATE; SEROTONIN PLASMA MEMBRANE TRANSPORT PROTEINS; TRYPTOPHAN;

EID: 76849100874     PISSN: 03010082     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.pneurobio.2009.04.005     Document Type: Review

References (262)

1. Aarts M.M., and Tymianski M. Molecular mechanisms underlying specificity of excitotoxic signaling in neurons. Curr. Mol. Med. 4 (2004) 137-147
2. Alberati-Giani D., Cesura A.M., Broger C., Warren W.D., Röver S., and Malherbe P. Cloning and functional expression of human kynurenine 3-monooxygenase. FEBS Lett. 410 (1997) 407-412
3. Alkondon M., Pereira E.F., Yu P., Arruda E.Z., Almeida L.E., Guidetti P., Fawcett W.P., Sapko M.T., Randall W.R., Schwarcz R., Tagle D.A., and Albuquerque E.X. Targeted deletion of the kynurenine aminotransferase II gene reveals a critical role of endogenous kynurenic acid in the regulation of synaptic transmission via alpha7 nicotinic receptors in the hippocampus. J. Neurosci. 24 (2004) 4635-4648
4. Amori L., Guidetti P., Pellicciari R., Kajii Y., and Schwarcz R. On the relationship between the two branches of the kynurenine pathway in the rat brain in vivo. J. Neurochem. 109 (2009) 316-325
5. Andre C., O'Connor J.C., Kelley K.W., Lestage J., Dantzer R., and Castanon N. Spatio-temporal differences in the profile of murine brain expression of proinflammatory cytokines and indoleamine 2,3-dioxygenase in response to peripheral lipopolysaccharide administration. J. Neuroimmunol. 200 (2008) 90-99
6. Archer F.J., and Mancall E.L. Cultured fibroblasts in Huntington's disease. I. Effects of l-glutamic acid. Arch. Neurol. 40 (1983) 19-23
7. Barbeau A., Chase T.N., and Paulson G.W. Huntington's Chorea (1973), Raven Press, New York
8. Beal M., Kowall N., Ellison D., Mazurek M., Swartz K., and Martin J. Replication of the neurochemical characteristics of Huntington's disease by quinolinic acid. Nature 321 (1986) 168-171
9. Beal M.F. Mechanisms of excitotoxicity in neurologic diseases. FASEB J. 6 (1992) 3338-3344
10. Beal M.F., Ferrante R.J., Swartz K.J., and Kowall N.W. Chronic quinolinic acid lesions in rats closely resemble Huntington's disease. J. Neurosci. 11 (1991) 1649-1659
11. Beal M.F., Kowall N.W., Swartz K.J., Ferrante R.J., and Martin J.B. Systemic approaches to modifying quinolinic acid striatal lesions in rats. J. Neurosci. 8 (1988) 3901-3908
12. Beal M.F., Matson W.R., Storey E., Milbury P., Ryan E.A., Ogawa T., and Bird E.D. Kynurenic acid concentrations are reduced in Huntington's disease cerebral cortex. J. Neurol. Sci. 108 (1992) 80-87
13. Beal M.F., Matson W.R., Swartz K.J., Gamache P.H., and Bird E.D. Kynurenine pathway measurements in Huntington's disease striatum: evidence for reduced formation of kynurenic acid. J. Neurochem. 55 (1990) 1327-1339
14. Belladonna M.L., Puccetti P., Orabona C., Fallarino F., Vacca C., Volpi C., Gizzi S., Pallotta M.T., Fioretti M.C., and Grohmann U. Immunosuppression via tryptophan catabolism: the role of kynurenine pathway enzymes. Transplantation 84 (2007) S17-S20
15. Bergman H., Wichmann T., and DeLong M.R. Reversal of experimental parkinsonism by lesions of the subthalamic nucleus. Science 249 (1990) 1436-1438
16. Bernheimer H., Birkmayer W., Hornykiewicz O., Jellinger K., and Seitelberger F. Brain dopamine and the syndromes of Parkinson and Huntington: clinical, morphological and neurochemical correlations. J. Neurol. Sci. 20 (1973) 415-455
17. Besancon E., Guo S., Lok J., Tymianski M., and Lo E.H. Beyond NMDA and AMPA glutamate receptors: emerging mechanisms for ionic imbalance and cell death in stroke. Trends Pharmacol. Sci. 29 (2008) 268-275
18. Bird E.D., and Iversen L.L. Huntington's chorea. Post-mortem measurement of glutamic acid decarboxylase, choline acetyltransferase and dopamine in basal ganglia. Brain 97 (1974) 457-472
19. Biziere K., and Coyle J.T. Effects of cortical ablation on the neurotoxicity and receptor binding of kainic acid in striatum. J. Neurosci. Res. 4 (1979) 383-398
20. Björklund H., Olson L., Dahl D., and Schwarcz R. Short- and long-term consequences of intracranial injections of the excitotoxin, quinolinic acid, as evidenced by GFA immunohistochemistry of astrocytes. Brain Res. 371 (1986) 267-277
21. Bonilla E., Prasad A.L.N., and Arrieta A. Huntington's disease: studies on brain free amino acids. Life Sci. 42 (1988) 1153-1158
22. Bossy-Wetzel E., Schwarzenbacher R., and Lipton S.A. Molecular pathways to neurodegeneration. Nat. Med. 10 Suppl. (2004) S2-S9
23. Bradford S.E., and Nadler J.V. Aspartate release from rat hippocampal synaptosomes. Neuroscience 128 (2004) 751-765
24. Breton J., Avanzi N., Magagnin S., Covini N., Magistrelli G., Cozzi L., and Isacchi A. Functional characterization and mechanism of action of recombinant human kynurenine 3-hydroxylase. Eur. J. Biochem. 267 (2000) 1092-1099
25. Bruno V., Battaglia G., Copani A., D'Onofrio M., Di Iorio P., De Blasi A., Melchiorri D., Flor P.J., and Nicoletti F. Metabotropic glutamate receptor subtypes as targets for neuroprotective drugs. J. Cereb. Blood Flow Metab. 21 (2001) 1013-1033
26. Bruyn G.W. Huntington's chorea. In: Vinken P.J., and Bruyn G.W. (Eds). Handbook of Clinical Neurology (1968), North-Holland, Amsterdam 298-377
27. Caldeira M.V., Melo C.V., Pereira D.B., Carvalho R., Correia S.S., Backos D.S., Carvalho A.L., Esteban J.A., and Duarte C.B. Brain-derived neurotrophic factor regulates the expression and synaptic delivery of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor subunits in hippocampal neurons. J. Biol. Chem. 282 (2007) 12619-12628
28. Campochiaro P., and Coyle J.T. Ontogenetic development of kainate neurotoxicity: correlates with glutamatergic innervation. Proc. Natl. Acad. Sci. U.S.A. 75 (1978) 2025-2029
29. Carpenedo R., Chiarugi A., Russi P., Lombardi G., Carla V., Pellicciari R., Mattoli L., and Moroni F. Inhibitors of kynurenine hydroxylase and kynureninase increase cerebral formation of kynurenate and have sedative and anticonvulsant activities. Neuroscience 61 (1994) 237-244
30. Carpenedo R., Meli E., Peruginelli F., Pellegrini-Giampietro D.E., and Moroni F. Kynurenine 3-mono-oxygenase inhibitors attenuate post-ischemic neuronal death in organotypic hippocampal slice cultures. J. Neurochem. 82 (2002) 1465-1471
31. Carpenedo R., Pittaluga A., Cozzi A., Attucci S., Galli A., Raiteri M., and Moroni F. Presynaptic kynurenate-sensitive receptors inhibit glutamate release. Eur. J. Neurosci. 13 (2001) 2141-2147
32. Chiarugi A., Cozzi A., Ballerini C., Massacesi L., and Moroni F. Kynurenine 3-mono-oxygenase activity and neurotoxic kynurenine metabolites increase in the spinal cord of rats with experimental allergic encephalomyelitis. Neuroscience 102 (2001) 687-695
33. Chiarugi A., Meli E., and Moroni F. Similarities and differences in the neuronal death processes activated by 3OH-kynurenine and quinolinic acid. J. Neurochem. 77 (2001) 1310-1318
34. Choi D.W. Glutamate neurotoxicity in cortical cell culture is calcium dependent. Neurosci. Lett. 58 (1985) 293-297
35. Choi D.W. NMDA receptors and AMPA/kainate receptors mediate parallel injury in cerebral cortical cultures subjected to oxygen-glucose deprivation. Prog. Brain Res. 96 (1993) 137-143
36. Ciaramitaro V.M., Wallace S.F., and Rosenquist A.C. Ibotenic acid lesions of the substantia nigra pars reticulata ipsilateral to a visual cortical lesion fail to restore visual orienting responses in the cat. J. Comp. Neurol. 377 (1997) 596-610
37. Clark C.J., Mackay G.M., Smythe G.A., Bustamante S., Stone T.W., and Phillips R.S. Prolonged survival of a murine model of cerebral malaria by kynurenine pathway inhibition. Infect. Immun. 73 (2005) 5249-5251
38. Comings D.E., Goetz I.E., Holden J., and Holtz J. Huntington disease and Tourette syndrome. II. Uptake of glutamic acid and other amino acids by fibroblasts. Am. J. Hum. Genet. 33 (1981) 175-186
39. Connick J.H., Carlá V., Moroni F., and Stone T.W. Increase in kynurenic acid in Huntington's disease motor cortex. J. Neurochem. 52 (1989) 985-987
40. Connor T.J., Starr N., O'Sullivan J.B., and Harkin A. Induction of indolamine 2,3-dioxygenase and kynurenine 3-monooxygenase in rat brain following a systemic inflammatory challenge: a role for IFN-gamma?. Neurosci. Lett. 441 (2008) 29-34
41. Coyle J.T. Glial metabolites of tryptophan and excitotoxicity: coming unglued. Exp. Neurol. 197 (2006) 4-7
42. Coyle J.T., Ferkany J.W., and Zaczek R. Kainic acid: insights from a neurotoxin into the pathophysiology of Huntington's disease. Neurobehav. Toxicol. Teratol. 5 (1983) 617-624
43. Coyle J.T., and Schwarcz R. Lesion of striatal neurones with kainic acid provides a model for Huntington's chorea. Nature 263 (1976) 244-246
44. Coyle J.T., Schwarcz R., Bennett J.P., and Campochiaro P. Clinical, neuropathologic and pharmacologic aspects of Huntington's disease: correlates with a new animal model. Prog. Neuropsychopharmacol. 1 (1977) 13-30
45. Cozzi A., Carpenedo R., and Moroni F. Kynurenine hydroxylase inhibitors reduce ischemic brain damage: studies with (m-nitrobenzoyl)-alanine (mNBA) and 3,4-dimethoxy-[-N-4-(nitrophenyl)thiazol-2yl]-benzenesulfonamide (Ro 61-8048) in models of focal or global brain ischemia. J. Cereb. Blood Flow Metab. 19 (1999) 771-777
46. Cross A.J., Slater P., and Reynolds G.P. Reducted high-affinity glutamate uptake sites in the brains of patients with Huntington's disease. Neurosci. Lett. 67 (1982) 198-202
47. Croucher M.J., Collins J.F., and Meldrum B.S. Anticonvulsant action of excitatory amino acid antagonists. Science 216 (1982) 899-901
48. Curtis D.R., Duggan A.W., Felix D., Johnston G.A.R., Tebecis A.K., and Watkins J.C. Excitation of mammalian central neurones by acidic amino acids. Brain Res. 41 (1972) 283-301
49. Curtis D.R., and Watkins J.C. The excitation and depression of spinal neurones by structurally related amino acids. J. Neurochem. 6 (1960) 117-141
50. Danbolt N.C. Glutamate uptake. Prog. Neurobiol. 65 (2001) 1-105
51. Davies J., Evans R.H., Francis A.A., and Watkins J.C. Excitatory amino acid receptors and synaptic excitation in the mammalian central nervous system. J. Physiol. 75 (1979) 641-654
52. Davies S.W., and Roberts P.J. Sparing of cholinergic neurons following quinolinic acid lesions of the rat striatum. Neuroscience 26 (1988) 387-393
53. De Carvalho L.P., Bochet P., and Rossier J. The endogenous agonist quinolinic acid and the non endogenous homoquinolinic acid discriminate between NMDAR2 receptor subunit. Neurochem. Int. 28 (1996) 445-452
54. Decker R.H., Brown R.R., and Price J.M. Studies on the biological activity of nicotinylalanine, an analogue of kynurenine. J. Biol. Chem. 238 (1963) 1049-1053
55. DiFiglia M. Excitotoxic injury of the neostriatum: a model for Huntington's disease. Trends Neurosci. 13 (1990) 286-289
56. Divac I., Markowitsch H.J., and Pritzel M. Behavioral and anatomical consequences of small intrastriatal injections of kainic acid in the rat. Brain Res. 151 (1978) 523-532
57. During M.J., Freese A., Heyes M.P., Swartz K.J., Markey S.P., Roth R.H., and Martin J.B. Neuroactive metabolites of l-tryptophan, serotonin and quinolinic acid, in striatal extracellular fluid. FEBS Lett. 247 (1989) 438-444
58. Eastman C.L., and Guilarte T.R. Cytotoxicity of 3-hydroxykynurenine in a neuronal hybrid cell line. Brain Res. 495 (1989) 225-231
59. Eastman C.L., and Guilarte T.R. The role of hydrogen peroxide in the in vitro cytotoxicity of 3-hydroxykynurenine. Neurochem. Res. 15 (1990) 1101-1107
60. Ellison D.W., Beal M.F., Mazurek M.F., Malloy J.R., Bird E.D., and Martin J.B. Amino acid neurotransmitter abnormalities in Huntington's disease and the quinolinic acid animal model of Huntington's disease. Brain 110 (1987) 1657-1673
61. Erhardt S., Oberg H., and Engberg G. Pharmacologically elevated levels of endogenous kynurenic acid prevent nicotine-induced activation of nigral dopamine neurons. Naunyn Schmiedebergs Arch. Pharmacol. 363 (2001) 21-27
62. 2O hydroxylation of l-[3,5-3H]kynurenine. Anal. Biochem. 205 (1992) 257-262
63. Eugster C.H. Active substances from the toadstool. Naturwissenschaften 55 (1968) 305-313
64. Fagni L., Lafon-Cazal M., Rondouin G., Manzoni O., Lerner-Natoli M., and Bockaert J. The role of free radicals in NMDA-dependent neurotoxicity. Prog. Brain Res. 103 (1994) 381-390
65. Fan M.M., and Raymond L.A. N-methyl-d-aspartate (NMDA) receptor function and excitotoxicity in Huntington's disease. Prog. Neurobiol. 81 (2007) 272-293
66. Ferkany J.W., Zaczek R., and Coyle J.T. Kainic acid stimulates excitatory amino acid neurotransmitter release at presynaptic receptors. Nature 298 (1982) 757-759
67. Ferrante R.J., Beal M.F., Kowall N.W., Richardson E.P., and Martin J.B. Sparing of acetylcholinesterase-containing striatal neurons in Huntington's disease. Brain Res. 411 (1987) 162-166
68. Ferrante R.J., and Kowall N.W. Tyrosine hydroxylase-like immunoreactivity is distributed in the matrix compartment of normal human and Huntington's disease striatum. Brain Res. 416 (1987) 141-146
69. Ferrante R.J., Kowall N.W., Beal M.F., Martin J.B., Bird E.D., and Richardson E.P.J. Morphologic and histochemical characteristics of a spared subset of striatal neurons in Huntington's disease. J. Neuropathol. Exp. Neurol. 46 (1987) 12-27
70. Ferrante R.J., Kowall N.W., Cipolloni P.B., Storey E., and Beal M.F. Excitotoxin lesions in primates as a model for Huntington's disease: histopathologic and neurochemical characterization. Exp. Neurol. 119 (1993) 46-71
71. Flicker C., Dean R.L., Watkins D.L., Fisher S.K., and Bartus R.T. Behavioral and neurochemical effects following neurotoxic lesions of a major cholinergic input to the cerebral cortex in the rat. Pharmacol. Biochem. Behav. 18 (1983) 973-981
72. Foster A.C., Collins J.F., and Schwarcz R. On the excitotoxic properties of quinolinic acid, 2,3-piperidine dicarboxylic acids and structurally related compounds. Neuropharmacology 22 (1983) 1331-1342
73. Foster A.C., and Schwarcz R. Characterization of quinolinic acid phosphoribosyltransferase in human blood and observations in Huntington's disease. J. Neurochem. 45 (1985) 199-205
74. Foster A.C., Vezzani A., French E.D., and Schwarcz R. Kynurenic acid blocks neurotoxicity and seizures induced in rats by the related brain metabolite quinolinic acid. Neurosci. Lett. 48 (1984) 273-278
75. Foster A.C., Whetsell Jr. W.O., Bird E.D., and Schwarcz R. Quinolinic acid phosphoribosyltransferase in human and rat brain: activity in Huntington's disease and in quinolinate-lesioned rat striatum. Brain Res. 336 (1985) 207-214
76. Foster A.C., White R.J., and Schwarcz R. Synthesis of quinolinic acid by 3-hydroxyanthranilic acid oxygenase in rat brain tissue in vitro. J. Neurochem. 47 (1986) 23-30
77. Foster A.C., Zinkand W.C., and Schwarcz R. Quinolinic acid phosphoribosyltransferase in rat brain. J. Neurochem. 44 (1985) 446-454
78. Fukui S., Schwarcz R., Rapoport S.I., Takada Y., and Smith Q.R. Blood-brain barrier transport of kynurenines: implications for brain synthesis and metabolism. J. Neurochem. 56 (1991) 2007-2017
79. Gál E.M., and Sherman A.D. l-Kynurenine: its synthesis and possible regulatory function in brain. Neurochem. Res. 5 (1980) 223-239
80. Garthwaite G., Hajos F., and Garthwaite J. Ionic requirements for neurotoxic effects of excitatory amino acid analogues in rat cerebellar slices. Neuroscience 18 (1986) 437-447
81. Gehrmann J., Matsumoto Y., and Kreutzberg G.W. Microglia: intrinsic immuneffector cell of the brain. Brain Res. Bull. 20 (1995) 269-287
82. Giorgini F. The kynurenine pathway and microglia: implications for pathology and therapy in Huntington's disease. In: Outeiro T. (Ed). Protein Misfolding in Biology and Disease (2008), Transworld Research Network, Kerala, India 231-255
83. Giorgini F., Guidetti P., Nguyen Q., Bennett S.C., and Muchowski P.J. A genomic screen in yeast implicates kynurenine 3-monooxygenase as a therapeutic target for Huntington disease. Nat. Gen. 37 (2005) 526-531
84. Giorgini F., Möller T., Kwan W., Zwilling D., Wacker J.L., Hong S., Tsai L.C., Cheah C.S., Schwarcz R., Guidetti P., and Muchowski P.J. Histone deacetylase inhibition modulates kynurenine pathway activation in yeast, microglia, and mice expressing a mutant huntingtin fragment. J. Biol. Chem. 283 (2008) 7390-7400
85. Goda K., Hamane Y., Kishimoto R., and Ogishi Y. Radical scavenging properties of tryptophan metabolites. Estimation of their radical reactivity. Adv. Exp. Med. Biol. 467 (1999) 397-402
86. Goldstein L.E., Leopold M.C., Huang X., Atwood C.S., Saunders A.J., Hartshorn M., Lim J.T., Faget K.Y., Muffat J.A., Scarpa R.C., Chylack L.T.J., Bowden E.F., Tanzi R.E., and Bush A.I. 3-Hydroxykynurenine and 3-hydroxyanthranilic acid generate hydrogen peroxide and promote α-crystallin cross-linking by metal ion reduction. Biochemistry 39 (2000) 7266-7275
87. Gonzalez A., Varo N., Alegre E., Diaz A., and Melero I. Immunosuppression routed via the kynurenine pathway: a biochemical and pathophysiologic approach. Adv. Clin. Chem. 45 (2008) 155-197
88. Greenamyre J.T., Penney J.B., Young A.B., D'Amato C.J., Hicks S.P., and Shoulson I. Alterations in l-glutamate binding in Alzheimer's and Huntington's diseases. Science 227 (1985) 1496-1499
89. Greenamyre J.T., Young A.B., and Penney J.B. Quantitative autoradiographic distribution of l-[3H]glutamate-binding sites in rat central nervous system. J. Neurosci. 4 (1984) 2133-2144
90. Greene J.G., and Greenamyre J.T. Bioenergetics and glutamate excitotoxicity. Prog. Neurobiol. 48 (1996) 613-634
91. Guidetti P., Bates G.P., Graham R.K., Hayden M.R., Leavitt B.R., MacDonald M.E., Slow E.J., Wheeler V.C., Woodman B., and Schwarcz R. Elevated brain 3-hydroxykynurenine and quinolinate levels in Huntington disease mice. Neurobiol. Dis. 23 (2006) 190-197
92. Guidetti P., Eastman C.L., and Schwarcz R. Metabolism of [5-3H]kynurenine in the rat brain in vivo: evidence for the existence of a functional kynurenine pathway. J. Neurochem. 65 (1995) 2621-2632
93. Guidetti P., Luthi-Carter R.E., Augood S.J., and Schwarcz R. Neostriatal and cortical quinolinate levels are increased in early grade Huntington's disease. Neurobiol. Dis. 17 (2004) 455-461
94. Guidetti P., Reddy P.H., Tagle D.A., and Schwarcz R. Early kynurenergic impairment in Huntington's disease and in a transgenic animal model. Neurosci. Lett. 283 (2000) 233-235
95. Guidetti P., and Schwarcz R. 3-Hydroxykynurenine potentiates quinolinate but not NMDA toxicity in the rat striatum. Eur. J. Neurosci. 11 (1999) 3857-3863
96. Guillemin G.J., Kerr S.J., Smythe G.A., Smith D.G., Kapoor V., Armati P.J., Croitoru J., and Brew B.J. Kynurenine pathway metabolism in human astrocytes: a paradox for neuronal protection. J. Neurochem. 78 (2001) 842-853
97. Hall J.G., Hicks T.P., McLennan H., Richardson T.L., and Wheal H.V. The excitation of mammalian central neurones by amino acids. J. Physiol. 286 (1979) 29-39
98. Hamann M., Sander S.E., and Richter A. Effects of the kynurenine 3-hydroxylase inhibitor Ro 61-8048 after intrastriatal injections on the severity of dystonia in the dt sz mutant. Eur. J. Pharmacol. 586 (2008) 156-159
99. Harris C., Miranda A., Tanguay J., Boegman R., Beninger R., and Jhamandas K. Modulation of striatal quinolinate neurotoxicity by elevation of endogenous brain kynurenic acid. Brit. J. Pharmacol. 124 (1998) 391-399
100. Hassel B., Tessler S., Faull R.L., and Emson P.C. Glutamate uptake is reduced in prefrontal cortex in Huntington's disease. Neurochem. Res. 33 (2008) 232-237
101. Heyes M.P., Achim C.L., Wiley C.A., Major E.O., Saito K., and Markey S.P. Human microglia convert l-tryptophan into the neurotoxin quinolinic acid. Biochem. J. 320 (1996) 595-597
102. Heyes M.P., Chen C.Y., Major E.O., and Saito K. Different kynurenine pathway enzymes limit quinolinic acid formation by various human cell types. Biochem. J. 326 (1997) 351-356
103. Heyes M.P., Garnett E.S., and Brown R.R. Normal excretion of quinolinic acid in Huntington's disease. Life Sci. 37 (1985) 1811-1816
104. Heyes M.P., Rubinow D., Lane C., and Markey S.P. Cerebrospinal fluid quinolinic acid concentrations are increased in acquired immune deficiency syndrome. Ann. Neurol. 26 (1989) 275-277
105. Heyes M.P., Saito K., Jacobowitz D., Markey S.P., Takikawa O., and Vickers J.H. Poliovirus induces indoleamine-2,3-dioxygenase and quinolinic acid synthesis in macaque brain. FASEB J. 6 (1992) 2977-2989
106. Heyes M.P., Saito K., Major E.O., Milstien S., Markey S.P., and Vickers J.H. A mechanism of quinolinic acid formation by brain in inflammatory neurological disease. Brain 116 (1993) 1425-1450
107. Heyes M.P., Swartz K.J., Markey S.P., and Beal M.F. Regional brain and cerebrospinal fluid quinolinic acid concentrations in Huntington's disease. Neurosci. Lett. 122 (1991) 265-269
108. Hilmas C., Pereira E.F., Alkondon M., Rassoulpour A., Schwarcz R., and Albuquerque E.X. The brain metabolite kynurenic acid inhibits alpha7 nicotinic receptor activity and increases non-alpha7 nicotinic receptor expression: physiopathological implications. J. Neurosci. 21 (2001) 7463-7473
109. Honoré T., Davies S.N., Drejer J., Fletcher E.J., Jacobsen P., Lodge D., and Nielsen F.E. Quinoxalinediones: potent competitive non-NMDA glutamate receptor antagonists. Science 241 (1988) 701-703
110. Honoré T., Lauridsen J., and Krogsgaard-Larsen P. The binding of [3H]AMPA, a structural analogue of glutamic acid, to rat brain membranes. J. Neurochem. 38 (1982) 173-178
111. Huntington's Disease Collaborative Research Group. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 72 (1993) 971-983
112. Huntington G. On chorea. Med. Surg. Rep. 26 (1872) 317-321
113. Isacson O., Brundin P., Kelly P.A., Gage F.H., and Björklund A. Functional neuronal replacement by grafted striatal neurones in the ibotenic acid-lesioned rat striatum. Nature 311 (1984) 458-460
114. Iwata H., Yamagami S., Mizuo H., and Baba A. Cysteine sulfinic acid in the central nervous system: uptake and release of cysteine sulfinic acid by a rat brain preparation. J. Neurochem. 38 (1982) 1268-1274
115. Jackson M., Gentleman S., Lennox G., Ward L., Gray T., Randall K., Morrell K., and Lowe J. The cortical neuritic pathology of Huntington's disease. Neuropathol. Appl. Neurobiol. 21 (1995) 18-26
116. Johnston M.V. Excitotoxicity in perinatal brain injury. Brain Pathol. 15 (2005) 234-240
117. Jonas P., and Spruston N. Mechanisms shaping glutamate-mediated excitatory postsynaptic currents in the CNS. Curr. Opin. Neurobiol. 4 (1994) 366-372
118. Kalia L.V., Kalia S.K., and Salter M.W. NMDA receptors in clinical neurology: excitatory times ahead. Lancet Neurol. 7 (2008) 742-755
119. Kessler M., Terramani T., Lynch G., and Baudry M. A glycine site associated with N-methyl-d-aspartic acid receptors: characterization and identification of a new class of antagonists. J. Neurochem. 52 (1989) 1319-1328
120. Kido R., and Noguchi T. Kynurenine pyruvate transaminase and its specific inhibitor in rat intestine. Acta Vitam. Enzyol. 29 (1975) 310-312
121. Kim J.S., Kornhuber H.H., Holzmüller B., Schmid-Burgk W., Mergner T., and Krzepinski G. Reduction of cerebrospinal fluid glutamic acid in Huntington's chorea and in schizophrenic patients. Arch. Psych. Nervenkr. 228 (1980) 7-10
122. Kiss C., Ceresoli-Borroni G., Guidetti P., Zielke C.L., Zielke H.R., and Schwarcz R. Kynurenate production by cultured human astrocytes. J. Neural. Transm. 110 (2003) 1-14
123. Kita T., Morrison P.F., Heyes M.P., and Markey S.P. Effects of systemic and central nervous system localized inflammation on the contributions of metabolic precursors to the l-kynurenine and quinolinic acid pools in brain. J. Neurochem. 82 (2002) 258-268
124. Klancnik J.M., Cuenod M., Gahwiler B.H., Jiang Z.P., and Do K.Q. Release of endogenous amino acids, including homocysteic acid and cysteine sulphinic acid, from rat hippocampal slices evoked by electrical stimulation of schaffer collateral-commissural fibres. Neuroscience 49 (1992) 557-570
125. Köhler C., Schwarcz R., and Fuxe K. Intrahippocampal injections of ibotenic acid provide histological evidence for a neurotoxic mechanism different from kainic acid. Neurosci. Lett. 15 (1979) 223-228
126. Lapin I.P. Stimulant and convulsive effects of kynurenines injected into brain ventricles in mice. J. Neural. Transm. 42 (1978) 37-43
127. Lehrmann E., Molinari A., Speciale C., and Schwarcz R. Immunohistochemical visualization of newly formed quinolinate in the normal and excitotoxically lesioned rat striatum. Exp. Brain Res. 141 (2001) 389-397
128. Leipnitz G., Schumacher C., Dalcin K.B., Scussiato K., Solano A., Funchal C., Dutra-Filho C.S., Wyse A.T., Wannmacher C.M., Latini A., and Wajner M. In vitro evidence for an antioxidant role of 3-hydroxykynurenine and 3-hydroxyanthranilic acid in the brain. Neurochem. Int. 50 (2007) 83-94
129. Leist M., Fava E., Montecucco C., and Nicotera P. Peroxynitrite and nitric oxide donors induce neuronal apoptosis by eliciting autocrine excitotoxicity. Eur. J. Neurosci. 9 (1997) 1488-1498
130. Lima S., Kumar S., Gawandi V., Momany C., and Phillips R.S. Crystal structure of the Homo sapiens kynureninase-3-hydroxyhippuric acid inhibitor complex: insights into the molecular basis of kynureninase substrate specificity. J. Med. Chem. 52 (2009) 389-396
131. Lopez A.S., Alegre E., LeMaoult J., Carosella E., and Gonzalez A. Regulatory role of tryptophan degradation pathway in HLA-G expression by human monocyte-derived dendritic cells. Mol. Immunol. 43 (2006) 2151-2160
132. Ma L., Morton A.J., and Nicholson L.F. Microglia density decreases with age in a mouse model of Huntington's disease. Glia 43 (2003) 274-280
133. Mangano R.M., and Schwarcz R. Platelet glutamate and aspartate uptake in Huntington's disease. J. Neurochem. 37 (1981) 1072-1074
134. Mangano R.M., and Schwarcz R. Huntington's disease. Glutamate and aspartate metabolism in blood platelets. J. Neurol. Sci. 53 (1982) 489-500
135. Mangiarini L., Sathasivam K., Seller M., Lawton M., Trottier Y., Lehrach H., Davies S.W., and Bates G.P. Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell 87 (1996) 493-506
136. Mason S.T., Sanberg P.R., and Fibiger H.C. Amphetamine-induced locomotor activity and stereotypy after kainic acid lesions of the striatum. Life Sci. 22 (1978) 451-460
137. Mattson M.P. Calcium and neurodegeneration. Aging Cell 6 (2007) 337-350
138. May P.C., and Gray P.N. l-Homocysteic acid as an alternative cytotoxin for studying glutamate-induced cellular degeneration of Huntington's disease and normal skin fibroblasts. Life Sci. 37 (1985) 1483-1489
139. McBean G.J., and Roberts P.J. Neurotoxicity of l-glutamate and dl-threo-3-hydroxyaspartate in the rat striatum. J. Neurochem. 44 (1985) 247-254
140. McDonald J.W., Silverstein F.S., and Johnston M.V. Neurotoxicity of N-methyl-d-aspartate is markedly enhanced in developing rat central nervous system. Brain Res. 459 (1988) 200-203
141. McGeer E.G., and McGeer P.L. Duplication of biochemical changes of Huntington's chorea by intrastriatal injections of glutamic and kainic acids. Nature 263 (1976) 517-519
142. McGeer E.G., McGeer P.L., and Singh K. Kainate-induced degeneration of neostriatal neurons: dependency upon corticostriatal tract. Brain Res. 139 (1978) 381-383
143. McGeer P.L., McGeer E.G., and Fibiger H.C. Choline acetylase and glutamic acid decarboxylase in Huntington's chorea. A preliminary study. Neurology 23 (1973) 912-917
144. Minghetti L., Greco A., Potenza R.L., Pezzola A., Blum D., Bantubungi K., and Popoli P. Effects of the adenosine A2A receptor antagonist SCH 58621 on cyclooxygenase-2 expression, glial activation, and brain-derived neurotrophic factor availability in a rat model of striatal neurodegeneration. J. Neuropathol. Exp. Neurol. 66 (2007) 363-371
145. Miranda A.F., Boegman R.J., Beninger R.J., and Jhamandas K. Protection against quinolinic acid-mediated excitotoxicity in nigrostriatal dopaminergic neurons by endogenous kynurenic acid. Neuroscience 78 (1997) 967-975
146. Monaghan D.T., and Beaton J.A. Quinolinate differentiates between forebrain and cerebellar NMDA receptors. Eur. J. Pharmacol. 194 (1991) 123-125
147. Monaghan D.T., Holets V.R., Toy D.W., and Cotman C.W. Anatomical distributions of four pharmacologically distinct 3H-l-glutamate binding sites. Nature 306 (1983) 176-179
148. Moroni F. Tryptophan metabolism and brain function: focus on kynurenine and other indole metabolites. Eur. J. Pharmacol. 375 (1999) 87-100
149. Moroni F., Russi P., Gallo-Mezo M.A., Moneti G., and Pellicciari R. Modulation of quinolinic and kynurenic acid content in the rat brain: effects of endotoxins and nicotinylalanine. J. Neurochem. 57 (1991) 1630-1635
150. Müller A.C., Dairam A., Limson J.L., and Daya S. Mechanisms by which acyclovir reduces the oxidative neurotoxicity and biosynthesis of quinolinic acid. Life Sci. 80 (2007) 918-925
151. Müller N., and Schwarz M.J. The immune-mediated alteration of serotonin and glutamate: towards an integrated view of depression. Mol. Psychiatry 12 (2007) 988-1000
152. Myers R.H., Vonsattel J.P., Paskevich P.A., Kiely D.K., Stevens T.J., Cupples L.A., Richardson Jr. E.P., and Bird E.D. Decreased neuronal and increased oligodendroglial densities in Huntington's disease caudate nucleus. J. Neuropathol. Exp. Neurol. 50 (1991) 729-742
153. Nadler J.V., Evenson D.A., and Cuthbertson G.J. Comparative toxicity of kainic acid and other acidic amino acids toward rat hippocampal neurons. Neuroscience 6 (1981) 2505-2517
154. Nakagami Y., Saito H., and Katsuki H. 3-Hydroxykynurenine toxicity on the rat striatum in vivo. Jpn. J. Pharmacol. 71 (1996) 183-186
155. Nakao N., Grasbon-Frodl E.M., Widner H., and Brundin P. Antioxidant treatment protects striatal neurons against excitotoxic insults. Neuroscience 73 (1996) 185-200
156. Németh H., Toldi J., and Vecsei L. Role of kynurenines in the central and peripheral nervous systems. Curr. Neurovasc. Res. 2 (2005) 249-260
157. Németh H., Toldi J., and Vecsei L. Kynurenines, Parkinson's disease and other neurodegenerative disorders: preclinical and clinical studies. J. Neural. Transm. 70 (2006) 285-304
158. Nicotera P., and Lipton S.A. Excitotoxins in neuronal apoptosis and necrosis. J. Cereb. Blood Flow Metab. 19 (1999) 583-591
159. O'Brien R.J., Lau L.F., and Huganir R.L. Molecular mechanisms of glutamate receptor clustering at excitatory synapses. Curr. Opin. Neurobiol. 8 (1998) 364-369
160. O'Connor, J.C., Lawson, M.A., Andre, C., Moreau, M., Lestage, J., Castanon, N., Kelley, K.W., Dantzer, R., 2008. Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice. Mol. Psych. (Epub).
161. Okamoto H., and Hayaishi O. Solubilization and partial purification of kynurenine hydroxylase from mitochondrial outer membrane and its electron donors. Arch. Biochem. Biophys. 131 (1969) 603-608
162. Okuda S., Nishiyama N., Saito H., and Katsuki H. Hydrogen peroxide-mediated neuronal cell death induced by an endogenous neurotoxin, 3-hydroxykynurenine. Proc. Natl. Acad. Sci. U.S.A. 93 (1996) 12553-12558
163. Okuda S., Nishiyama N., Saito H., and Katsuki H. 3-Hydroxykynurenine, an endogenous oxidative stress generator, causes neuronal cell death with apoptotic features and region selectivity. J. Neurochem. 70 (1998) 299-307
164. Olney J.W. Toxic effects of glutamate and related amino acids on the developing central nervous system. In: Nyhan W.H. (Ed). Heritable Disorders of Amino Acid Metabolism (1974), John Wiley, New York 501-512
165. Olney J.W., and de Gubareff T. Extreme sensitivity of olfactory cortical neurons to kainic acid toxicity. In: McGeer E.G., Olney J.W., and McGeer P.L. (Eds). Kainic Acid as a Tool in Neurobiology (1978), Raven Press, New York 201-217
166. Olney J.W., and de Gubareff T. Glutamate neurotoxicity and Huntington's chorea. Nature 271 (1978) 557-559
167. Olney J.W., de Gubareff T., and Labruyere J. Alpha-aminoadipate blocks the neurotoxic action of N-methyl aspartate. Life Sci. 25 (1979) 537-540
168. Olney J.W., Fuller T., and de Gubareff T. Acute dendrotoxic changes in the hippocampus of kainate treated rats. Brain Res. 176 (1979) 91-100
169. Olney J.W., Ho O.L., and Rhee V. Cytotoxic effects of acidic and sulphur containing amino acids on the infant mouse central nervous system. Exp. Brain Res. 14 (1971) 61-76
170. Olney J.W., Labruyere J., Collins J.F., and Curry K. D-aminaphosphonovalerate is 100-fold more powerful than d-alpha-aminoadipate in blocking N-methylaspartate neurotoxicity. Brain Res. 221 (1981) 207-210
171. Olney J.W., Misra C.H., and de Gubareff T. Cysteine-S-sulfate: brain damaging metabolite in sulfite oxidase deficiency. J. Neuropathol. Exp. Neurol. 34 (1975) 167-177
172. Olney J.W., Price M.T., Salles K.S., Labruyere J., Ryerson R., Mahan K., Frierdich G., and Samson L. l-Homocysteic acid: an endogenous excitotoxic ligand of the NMDA receptor. Brain Res. Bull. 19 (1987) 597-602
173. Olney J.W., Rhee V., and Ho O.L. Kainic acid: a powerful neurotoxic analogue of glutamate. Brain Res. 77 (1974) 507-512
174. Olney J.W., and Sharpe L.G. Brain lesions in an infant rhesus monkey treated with monsodium glutamate. Science 166 (1969) 386-388
175. Oxenkrug G.F. Genetic and hormonal regulation of tryptophan kynurenine metabolism: implications for vascular cognitive impairment, major depressive disorder, and aging. Ann. NY Acad. Sci. 1122 (2007) 35-49
176. Pearson S.J., Meldrum A., and Reynolds G.P. An investigation of the activities of 3-hydroxykynureninase and kynurenine aminotransferase in the brain of Huntington's disease. J. Neural. Transm. 102 (1995) 67-73
177. Pearson S.J., and Reynolds G.P. Determination of 3-hydroxykynurenine in human brain and plasma by high-performance liquid chromatography with electrochemical detection. J. Chromatogr. 565 (1991) 436-440
178. Pearson S.J., and Reynolds G.P. Increased brain concentrations of a neurotoxin, 3-hydroxykynurenine, in Huntington's disease. Neurosci. Lett. 144 (1992) 199-201
179. Pellegrini-Giampietro D.E., Pulsinelli W.A., and Zukin R.S. NMDA and non-NMDA receptor gene expression following global brain ischemia in rats: effect of NMDA and non-NMDA receptor antagonists. J. Neurochem. 62 (1994) 1067-1073
180. Pellicciari R., Natalini B., Costantino G., Mahmoud M.R., Mattoli L., Sadeghpour B.M., Moroni F., Chiarugi A., and Carpenedo R. Modulation of the kynurenine pathway in search for new neuroprotective agents. Synthesis and preliminary evaluation of (m-nitrobenzoyl)alanine, a potent inhibitor of kynurenine-3-hydroxylase. J. Med. Chem. 37 (1994) 647-655
181. Pérez-De La Cruz V., González-Cortés C., Galván-Arzate S., Medina-Campos O.N., Pérez-Severiano F., Ali S.F., Pedraza-Chaverrí J., and Santamaría A. Excitotoxic brain damage involves early peroxynitrite formation in a model of Huntington's disease in rats: protective role of iron porphyrinate 5,10,15,20-tetrakis (4-sulfonatophenyl)porphyrinate iron(III). Neuroscience 135 (2005) 463-474
182. Pérez-De La Cruz V., and Santamaria A. Integrative hypothesis for Huntington's disease: a brief review of experimental evidence. Physiol. Res. 56 (2007) 513-526
183. Perry T.L., and Hansen S. What excitotoxin kills striatal neurons in Huntington's disease? Clues from neurochemical studies. Neurology 40 (1990) 20-24
184. Plaitakis A., Berl S., and Yahr M.D. Abnormal glutamate metabolism in an adult-onset degenerative neurological disorder. Science 216 (1982) 193-196
185. Pláteník J., Stopka P., Vejrazka M., and Stípek S. Quiniolinic acid-iron(II) complexes: slow autoxidation, but enhanced hydroxyl radical production in the fenton reaction. Free Radic. Res. 34 (2001) 445-459
186. Rassoulpour A., Wu H.Q., Ferré S., and Schwarcz R. Nanomolar concentrations of kynurenic acid reduce extracellular dopamine levels in the striatum. J. Neurochem. 93 (2005) 762-765
187. Reiner A., Del Mar N., Deng Y.P., Meade C.A., Sun Z., and Goldowitz D. R6/2 neurons with intranuclear inclusions survive for prolonged periods in the brains of chimeric mice. J. Comp. Neurol. 505 (2007) 603-629
188. Reinhard Jr. J.F. Pharmacological manipulation of brain kynurenine metabolism. Ann. NY Acad. Sci. 1035 (2004) 335-349
189. Reinhard Jr. J.F., and Erickson J.B. Quinolinic acid in neurological disease: opportunities for novel drug discovery. Adv. Pharmacol. 30 (1994) 85-127
190. Reynolds G.P., Pearson S.J., Halket J., and Sandler M. Brain quinolinic acid in Huntington's disease. J. Neurochem. 50 (1988) 1959-1960
191. Rios C., and Santamaria A. Quinolinic acid is a potent lipid peroxidant in rat brain homogenates. Neurochem. Res. 16 (1991) 1139-1143
192. Roberts R.C., Du F., McCarthy K.E., Okuno E., and Schwarcz R. Immunocytochemical localization of kynurenine aminotransferase in the rat striatum: a light and electron microscopic study. J. Comp. Neurol. 326 (1992) 82-90
193. Rosas H.D., Salat D.H., Lee S.Y., Zaleta A.K., Hevelone N., and Hersch S.M. Complexity and heterogeneity: what drives the ever-changing brain in Huntington's disease?. Ann. NY Acad. Sci. 1147 (2008) 196-205
194. Röver S., Cesura A.M., Huguenin P., Kettler R., and Szente A. Synthesis and biochemical evaluation of N-(4-phenylthiazol-2-yl)benzenesulfonamides as high-affinity inhibitors of kynurenine 3-hydroxylase. J. Med. Chem. 40 (1997) 4378-4385
195. Ruddick J.P., Evans A.K., Nutt D.J., Lightman S.L., Rook G.A., and Lowry C.A. Tryptophan metabolism in the central nervous system: medical implications. Expert Rev. Mol. Med. 8 (2006) 1-27
196. Sacco R.L., DeRosa J.T., Haley E.C., Levin B., Ordronneau P., Phillips S.J., Rundek T., Snipes R.G., and Thompson J.L.P. Glycine antagonist in neuroprotection for patients with acute stroke. JAMA 285 (2001) 1719-1728
197. Saito K., Lackner A., Markey S.P., and Heyes M.P. Cerebral cortex and lung indoleamine-2,3-dioxygenase activity is increased in type-D retrovirus infected macaques. Brain Res. 540 (1991) 353-356
198. Saito K., Nowak Jr. T.S., Markey S.P., and Heyes M.P. Mechanism of delayed increases in kynurenine pathway metabolism in damaged brain regions following transient cerebral ischemia. J. Neurochem. 60 (1993) 180-192
199. Salt T.E., and Eaton S.A. Functions of ionotropic and metabotropic glutamate receptors in sensory transmission in the mammalian thalamus. Prog. Neurobiol. 48 (1996) 55-72
200. Samuel D., Errami M., and Nieoullon A. Localization of N-methyl-d-aspartate receptors in the rat striatum: effects of specific lesions on the [3H]3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid binding. J. Neurochem. 54 (1990) 1926-1933
201. Sanberg P.R., Pisa M., and Fibiger H.C. Avoidance, operant and locomotor behavior in rats with neostriatal injections of kainic acid. Pharmacol. Biochem. Behav. 10 (1979) 137-144
202. Santamaría A., Jiménez-Capdeville M.E., Camacho A., Rodríguez-Martínez E., Flores A., and Galván-Arzate S. In vivo hydroxyl radical formation after quinolinic acid infusion into rat corpus striatum. Neuroreport 12 (2001) 2693-2696
203. Santamaría A., and Ríos C. MK-801, an N-methyl-d-aspartate receptor antagonist, blocks quinolinic acid-induced lipid peroxidation in rat corpus striatum. Neurosci. Lett. 159 (1993) 51-54
204. Santiago-López D., Vázquez-Román B., Pérez-de La Cruz V., Barrera D., Rembao D., Salinas-Lara C., Pedraza-Chaverrí J., Galván-Arzate S., Ali S.F., and Santamaría A. Peroxynitrite decomposition catalyst, iron metalloporphyrin, reduces quinolinate-induced neurotoxicity in rats. Synapse 54 (2004) 233-238
205. Sapko M.T., Guidetti P., Yu P., Tagle D.A., Pellicciari R., and Schwarcz R. Endogenous kynurenate controls the vulnerability of striatal neurons to quinolinate: implications for Huntington's disease. Exp. Neurol. 197 (2006) 31-40
206. Sapp E., Kegel K.B., Aronin N., Hashikawa T., Uchiyama Y., Tohyama K., Bhide P.G., Vonsattel J.P., and DiFiglia M. Early and progressive accumulation of reactive microglia in the Huntington disease brain. J. Neuropathol. Exp. Neurol. 60 (2001) 161-172
207. Savvateeva E., Popov A., Kamyshev N., Bragina J., Heisenberg M., Senitz D., Kornhuber J., and Riederer P. Age-dependent memory loss, synaptic pathology and altered brain plasticity in the drosophila mutant cardinal accumulating 3-hydroxykynurenine. J. Neural. Transm. 107 (2000) 581-601
208. Schlossberger H.G., Kochen W., Linzen B., and Steinhart H. Progress in Tryptophan and Serotonin Research (1984), Walter de Gruyter, Berlin
209. Schröcksnadel K., Wirleitner B., Winkler C., and Fuchs D. Monitoring tryptophan metabolism in chronic immune activation. Clin. Chim. Acta 364 (2006) 82-90
210. Schwarcz R., Collins J.F., and Parks D.A. Alpha-amino-omega-phosphono carboxylates block ibotenate but not kainate neurotoxicity in rat hippocampus. Neurosci. Lett. 33 (1982) 85-90
211. Schwarcz R., and Coyle J.T. Striatal lesions with kainic acid: neurochemical characteristics. Brain Res. 127 (1977) 235-249
212. Schwarcz R., Creese I., Coyle J.T., and Snyder S.H. Dopamine receptors localised on cerebral cortical afferents to rat corpus striatum. Nature 271 (1978) 766-768
213. Schwarcz R., Foster A.C., French E.D., Whetsell Jr. W.O., and Köhler C. Excitotoxic models for neurodegenerative disorders. Life Sci. 35 (1984) 19-32
214. Schwarcz R., and Fuxe K. 3H-kainic acid binding: relevance for evaluating the neurotoxicity of kainic acid. Life Sci. 24 (1979) 1471-1480
215. Schwarcz R., Fuxe K., Agnati L.F., Hökfelt T., and Coyle J.T. Rotational behaviour in rats with unilateral striatal kainic acid lesions: a behavioural model for studies on intact dopamine receptors. Brain Res. 170 (1979) 485-495
216. Schwarcz R., Fuxe K., Hökfelt T., Andersson K., and Coyle J.T. Dopamine and Huntington's disease: assessment using the kainic acid model. In: Fuxe K., and Calne D.B. (Eds). Dopaminergic Ergot Derivatives and Motor Function (1979), Pergamon Press, New York 115-125
217. Schwarcz R., Hökfelt T., Fuxe K., Jonsson G., Goldstein M., and Terenius L. Ibotenic acid-induced neuronal degeneration: a morphological and neurochemical study. Exp. Brain Res. 37 (1979) 199-216
218. Schwarcz R., and Köhler C. Differential vulnerability of central neurons of the rat to quinolinic acid. Neurosci. Lett. 38 (1983) 85-90
219. Schwarcz R., and Meldrum B. Excitatory aminoacid antagonists provide a therapeutic approach to neurological disorders. Lancet 2 (1985) 140-143
220. Schwarcz R., Okuno E., and White R.J. Basal ganglia lesions in the rat: effects on quinolinic acid metabolism. Brain Res. 490 (1989) 103-109
221. Schwarcz R., Okuno E., White R.J., Bird E.D., and Whetsell Jr. W.O. 3-Hydroxyanthranilate oxygenase activity is increased in the brains of Huntington disease victims. Proc. Natl. Acad. Sci. U.S.A. 85 (1988) 4079-4081
222. Schwarcz R., and Pellicciari R. Manipulation of brain kynurenines: glial targets, neuronal effects, and clinical opportunities. J. Pharmacol. Exp. Ther. 303 (2002) 1-10
223. Schwarcz R., Tamminga C.A., Kurlan R., and Shoulson I. Cerebrospinal fluid levels of quinolinic acid in Huntington's disease and schizophrenia. Ann. Neurol. 24 (1988) 580-582
224. Schwarcz R., Whetsell Jr. W.O., and Mangano R.M. Quinolinic acid: an endogenous metabolite that produces axon-sparing lesions in rat brain. Science 219 (1983) 316-318
225. Seeburg P.H. The TINS/TIPS lecture-the molecular biology of mammalian glutamate receptor channels. Trends Neurosci. 16 (1993) 359-365
226. Sharpe N.A., and Tepper J.M. Postnatal development of excitatory synaptic input to the rat neostriatum: an electron microscopic study. Neuroscience 84 (1998) 1163-1175
227. Sheardown M.J., Nielsen E.O., Hansen A.J., Jacobsen P., and Honoré T. 2,3-Dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline: a neuroprotectant for cerebral ischemia. Science 247 (1990) 571-574
228. Simmons D.A., Casale M., Alcon B., Pham N., Narayan N., and Lynch G. Ferritin accumulation in dystrophic microglia is an early event in the development of Huntington's disease. Glia 55 (2007) 1074-1084
229. Simon R.P., Swan J.H., Griffiths T., and Meldrum B.S. Blockade of N-methyl-d-aspartate receptors may protect against ischemic damage in the brain. Science 226 (1984) 850-852
230. Singhrao S.K., Neal J.W., Morgan B.P., and Gasque P. Increased complement biosynthesis by microglia and complement activation on neurons in Huntington's disease. Exp. Neurol. 159 (1999) 362-376
231. Singhrao S.K., Thomas P., Wood J.D., MacMillan J.C., Neal J.W., Harper P.S., and Jones A.L. Huntingtin protein colocalizes with lesions of neurodegenerative diseases: an investigation in Huntington's, Alzheimer's, and Pick's diseases. Exp. Neurol. 150 (1998) 213-222
232. Slow E.J., van Raamsdonk J., Rogers D., Coleman S.H., Graham R.K., Deng Y., Oh R., Bissada N., Hossain S.M., Yang Y.Z., Li X.J., Simpson E.M., Gutekunst C.A., Leavitt B.R., and Hayden M.R. Selective striatal neuronal loss in a YAC128 mouse model of Huntington disease. Hum. Mol. Genet. 12 (2003) 1555-1567
233. Speciale C., and Schwarcz R. Uptake of kynurenine into rat brain slices. J. Neurochem. 54 (1990) 156-163
234. Speciale C., Wu H.Q., Cini M., Marconi M., Varasi M., and Schwarcz R. (R,S)-3,4-dichlorobenzoylalanine (FCE 28833A) causes a large and persistent increase in brain kynurenic acid levels in rats. Eur. J. Pharmacol. 315 (1996) 263-267
235. Stachowski E., Sathyasaikumar K.V., Guidetti P., Muchowski P.J., and Schwarcz R. Dysfunction of kynurenine pathway metabolism in the R6/2 mouse model of Huntington's disease. Soc. Neurosci. Abstr. 33 (2008) 642.20
236. Stahl W.L., Ward C.B., Casper J.B., and Bird T.D. Effects of l-glutamate on viabilities of cultured diploid skin fibroblasts and lymphocytes increased toxicity not observed in Huntington's disease. J. Neurol. Sci. 66 (1984) 183-191
237. Steiner H.X., McBean G.J., Köhler C., Roberts P.J., and Schwarcz R. Ibotenate-induced neuronal degeneration in immature rat brain. Brain Res. 307 (1984) 117-124
238. Stípek S., Stastný F., Pláteník J., Crkovská J., and Zima T. The effect of quinolinate on rat brain lipid peroxidation is dependent on iron. Neurochem. Int. 30 (1997) 233-237
239. Stoll L., Hall J., Van Buren N., Hall A., Knight L., Morgan A., Zuger S., Van Deusen H., and Gentile L. Differential regulation of ionotropic glutamate receptors. Biophys. J. 92 (2007) 1343-1349
240. Stone T.W., and Darlington L.G. Endogenous kynurenines as targets for drug discovery and development. Nat. Rev. Drug Discov. 1 (2002) 609-620
241. Stone T.W., and Perkins M.N. Quinolinic acid: a potent endogenous excitant at amino acid receptors in CNS. Eur. J. Pharmacol. 72 (1981) 411-412
242. Stoy N., Mackay G.M., Forrest C.M., Christofides J., Egerton M., Stone T.W., and Darlington L.G. Tryptophan metabolism and oxidative stress in patients with Huntington's disease. J. Neurochem. 93 (2005) 611-623
243. Swartz K.J., During M.J., Freese A., and Beal M.F. Cerebral synthesis and release of kynurenic acid: an endogenous antagonist of excitatory amino acid receptors. J. Neurosci. 10 (1990) 2965-2973
244. Tai Y.F., Pavese N., Gerhard A., Tabrizi S.J., Barker R.A., Brooks D.J., and Piccini P. Microglial activation in presymptomatic Huntington's disease gene carriers. Brain 130 (2007) 1759-1766
245. Tsai G., Gastfriend D.R., and Coyle J.T. The glutamatergic basis of human alcoholism. Am. J. Psychiat. 152 (1995) 332-340
246. Uemura T., and Hirai K. l-Kynurenine 3-monooxygenase from mitochondrial outer membrane of pig liver: purification, some properties, and monoclonal antibodies directed to the enzyme. J. Biochem. 123 (1998) 253-262
247. Ungerstedt U. Striatal dopamine release after amphetamine or nerve degeneration revealed by rotational behaviour. Acta Physiol. Scand. Suppl. 367 (1971) 49-68
248. Valko M., Leibfritz D., Moncol J., Cronin M.T., Mazur M., and Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int. J. Biochem. Cell Biol. 39 (2007) 44-84
249. Vazquez S., Garner B., Sheil M.M., and Truscott R.J. Characterisation of the major autoxidation products of 3-hydroxykynurenine under physiological conditions. Free Radic. Res. 32 (2000) 11-23
250. Villmann C., and Becker C.M. On the hypes and falls in neuroprotection: targeting the NMDA receptor. Neuroscientist 13 (2007) 594-615
251. Vincent S.R., and McGeer E.G. Kainic acid binding to membranes of striatal neurons. Life Sci. 24 (1979) 265-270
252. Vonsattel J.P., Myers R.H., Stevens T.J., Ferrante R.J., Bird E.D., and Richardson E.P.J. Neuropathological classification of Huntington's disease. J. Neuropathol. Exp. Neurol. 44 (1985) 559-577
253. Walsh J.L., Wu H.Q., Ungerstedt U., and Schwarcz R. 4-Chloro-3-hydroxyanthranilate inhibits quinolinate production in the rat hippocampus in vivo. Brain Res. Bull. 33 (1994) 513-516
254. Wenk G.L. A primate model of Alzheimer's disease. Behav. Brain Res. 57 (1993) 117-122
255. Wenk G.L., Cribbs B., and McCall L. Nucleus basalis magnocellularis: optimal coordinates for selective reduction of choline acetyltransferase in frontal neocortex by ibotenic acid injections. Exp. Brain Res. 56 (1984) 335-340
256. Wheeler V.C., White J.K., Gutekunst C.A., Vrbanac V., Weaver M., Li X.J., Li S.H., Yi H., Vonsattel J.P., Gusella J.F., Hersch S., Auerbach W., Joyner A.L., and MacDonald M.E. Long glutamine tracts cause nuclear localization of a novel form of huntingtin in medium spiny striatal neurons in HdhQ92 and HdhQ111 knock-in mice. Hum. Mol. Genet. 9 (2000) 503-513
257. Whetsell Jr. W.O., and Schwarcz R. Prolonged exposure to submicromolar concentrations of quinolinic acid causes excitotoxic damage in organotypic cultures of rat corticostriatal system. Neurosci. Lett. 97 (1989) 271-275
258. Wieloch T. Hypoglycemia-induced neuronal damage prevented by an N-methyl-d-aspartate antagonist. Science 230 (1985) 681-683
259. Wolfensberger M., Amsler U., Cuénod M., Foster A.C., Whetsell Jr. W.O., and Schwarcz R. Identification of quinolinic acid in rat and human brain tissue. Neurosci. Lett. 41 (1983) 247-252
260. Wu H.Q., Guidetti P., Goodman J.H., Varasi M., Ceresoli-Borroni G., Speciale C., Scharfman H.E., and Schwarcz R. Kynurenergic manipulations influence excitatory synaptic function and excitotoxic vulnerability in the rat hippocampus in vivo. Neuroscience 97 (2000) 243-251
261. Wyttenbach A., Sauvageot O., Carmichael J., Diaz-Latoud C., Arrigo A.P., and Rubinsztein D.C. Heat shock protein 27 prevents cellular polyglutamine toxicity and suppresses the increase of reactive oxygen species caused by huntingtin. Hum. Mol. Genet. 11 (2002) 1137-1151
262. Xu H., Zhang G.X., Ciric B., and Rostami A. IDO: a double-edged sword for T(H)1/T(H)2 regulation. Immunol. Lett. 121 (2008) 1-6