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Alterations in dopamine and glutamate neurotransmission in tetrahydrobiopterin deficient spr-/- mice: relevance to schizophrenia

  • Choi, Yong-Kee (Mailman Research Center, McLean Division of Massachusetts General Hospital, Belmont, Department of Psychiatry and Neuroscience Program, Harvard Medical School) ;
  • Tarazi, Frank I. (Mailman Research Center, McLean Division of Massachusetts General Hospital, Belmont, Department of Psychiatry and Neuroscience Program, Harvard Medical School)
  • Received : 2010.08.10
  • Published : 2010.09.30
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Abstract

Tetrahydrobiopterin ($BH_4$) is a pivotal cofactor for enzymes responsible for the synthesis and release of monoamine neurotransmitters including dopamine and serotonin as well as the release of glutamate. Deficiencies in $BH_4$ levels and reduced activities of $BH_4$-associated enzymes have been recently reported in patients with schizophrenia. Accordingly, it is possible that abnormalities in the biochemical cascades regulated by $BH_4$ may alter DA, 5-HT and Glu neurotransmission, and consequently contribute to the pathophysiology of different neuropsychiatric diseases including schizophrenia. The development of a novel strain of mutant mice that is deficient in $BH_4$ by knocking out the expression of a functional sepiapterin reductase gene (spr -/-) has added new insights into the potential role of $BH_4$ in the pathophysiology and improved treatment of schizophrenia.

Keywords

References

  1. Baldessarini, R. J. (1977) Schizophrenia. N. Engl. J. Med. 297, 988-995. https://doi.org/10.1056/NEJM197711032971807
  2. Nasrallah, H. A. and Weinberger, D. R. (1985) The Neurology of schizophrenia. Elsevier Science Publishers, Amsterdam, Netherlands.
  3. Tamminga, C. A. and Schulz, S. C. (1991) Advances in neuropsychiatry and psychopharmacology: schizophrenia research. Raven Press, New York, USA.
  4. Kandel, E. R. (2000) Disorders of thought and volition: Schizophrenia; in Kandel, E. R, Schwartz, J. H, Jessell, T. M, (eds.) Principles of neural science, pp.1188-1208. Elsevier, New York, USA.
  5. Weinberger, D. R. (1987) Implications of normal brain development for the pathogenesis of schizophrenia. Arch. Gen. Psychiatry 44, 660-669. https://doi.org/10.1001/archpsyc.1987.01800190080012
  6. Meltzer, H. Y. (1989) Clinical studies on the mechanism of action of clozapine: the dopamine-serotonin hypothesis of schizophrenia. Psychopharmacology 99, S18-27. https://doi.org/10.1007/BF00442554
  7. Davis, K., Kahn, R., Ko, G. and Davidson, M. (1991) Dopamine in schizophrenia: a review and reconceptualization. Am. J. Psychiatry 148, 1474-1486. https://doi.org/10.1176/ajp.148.11.1474
  8. Goff, D. C. and Coyle, J. T. (2001) The emerging role of glutamate in the pathophysiology and treatment of schizophrenia. Am. J. Psychiatry 158, 1367-1377. https://doi.org/10.1176/appi.ajp.158.9.1367
  9. Creese. I., Burt, D. R. and Snyder, S. H. (1976) Dopamine receptor binding predicts clinical and pharmacological potencies of antischizohrenic drugs. Science 192, 481-483. https://doi.org/10.1126/science.3854
  10. Angrist, B. M. and Gershon, S. (1970) The phenomenology of experimentally induced amphetamine psychosispreliminary observations. Biol. Psychiatry 2, 95-107.
  11. Lieberman, J. A., Kane, J. M. and Alvir, J. (1987) Provocative tests with psychostimulant drugs in schizophrenia. Psychopharmacology 91, 415-433. https://doi.org/10.1007/BF00216006
  12. Seeman, P. (1980) Brain dopamine receptors. Pharmacol. Rev. 32, 229-313.
  13. Seeman, P. (1992) Dopamine receptor sequences. Therapeutic levels of neuroleptics occupy D2 receptors, clozapine occupies D4. Neuropsychopharmacol. 7, 261-285.
  14. Wong, D. F., Wagner, H. N. Jr., Tune, L. E., Dannals, R. F., Pearlson, G. D., Links, J. M., Tamminga, C. A., Broussolle, E. P., Ravert, H. T., Wilson, A. A., Toung, J. K. T., Malat, J., Williams, J. A., O'Tuama, L. A., Snyder, S. H., Kuhar, M. J. and Gjedde, A. (1986) Positron emission tomography reveals elevated D2 dopamine receptors in drug-naive schizophrenics. Science 234, 1558-1563. https://doi.org/10.1126/science.2878495
  15. Farde, L., Wiesel, F. A., Stone-Elander, S., Halldin, C., Nordstrom, A. L., Hall, H. and Sedvall, G. (1990) $D_2$ dopamine receptors in neuroleptic-naive schizophrenic patients. A positron emission tomography study with ($^{11}C$) raclopride. Arch. Gen. Psychiatry. 47, 213-219. https://doi.org/10.1001/archpsyc.1990.01810150013003
  16. Hietala, J., Syvalahti, E., Vuorio, K., Nagren, K., Lehikoinen, P., Routsalainen, U., Rakkolainen, V., Lehtinen, V. and Wegelius, U. (1994) Striatal D2 dopamine receptor characteristics in neuroleptic-naive schizophrenic patients studied with positron emission tomography. Arch. Gen. Psychiatry 51, 116-123. https://doi.org/10.1001/archpsyc.1994.03950020040004
  17. Tarazi, F. I., Florijn, W. J. and Creese, I. (1997) Differential regulation of dopamine receptors after chronic typical and atypical antipsychotic drug treatment. Neuroscience 78, 985-996. https://doi.org/10.1016/S0306-4522(96)00631-8
  18. Tarazi, F. I., Zhang, K. and Baldessarini, R. J. (2001) Longterm effects of olanzapine, risperidone, and quetiapine on dopamine receptor types in regions of rat brain: implications for antipsychotic drug treatment. J. Pharmacol. Exp. Ther. 297, 711-717.
  19. Moran-Gates, T., Gan, L., Park, Y. S., Zhang, K., Baldessarini, R. J. and Tarazi, F. I. (2006) Repeated antipsychotic drug exposure in developing rats: dopamine receptor effects. Synapse 59, 92-100. https://doi.org/10.1002/syn.20220
  20. Moran-Gates, T., Grady, C., Park YS, Baldessarini, R. J. and Tarazi, F. I. (2007) Effects of risperidone on dopamine receptor subtypes in developing rat brain. Eur. Neuropsychopharmacol. 17, 448-555. https://doi.org/10.1016/j.euroneuro.2006.10.004
  21. Tsai, G. and Coyle, J. T. (2002) Glutamatergic mechanisms in schizophrenia. Ann. Rev. Pharmacol. Toxicol. 42, 165-179. https://doi.org/10.1146/annurev.pharmtox.42.082701.160735
  22. Javitt, D. C. and Zukin, S. R. (1991) Recent advances in the phencyclidine model of schizophrenia. Am. J. Psychiatry 148, 1301-1308. https://doi.org/10.1176/ajp.148.10.1301
  23. Moller, P. and Husby, R. (2000) The initial prodrome in schizophrenia: searching for naturalistic core dimensions of experience and behavior. Schizophr. Bull. 26, 217-232. https://doi.org/10.1093/oxfordjournals.schbul.a033442
  24. Silver, H., Feldman, P., Bilker, W. and Gur, R. C. (2003) Working memory deficit as a core neuropsychological dysfunction in schizophrenia. Am. J. Psychiatry 160, 1809-1816. https://doi.org/10.1176/appi.ajp.160.10.1809
  25. Mohn, A. R., Gainetdinov, R. R., Caron, M. G. and Koller, B. H. (1999) Mice with reduced NMDA receptor expression display behaviors related to schizophrenia. Cell 98, 427-436. https://doi.org/10.1016/S0092-8674(00)81972-8
  26. Meador-Woodruff, J. H. and Healy, D. J. (2000) Glutamate receptor expression in schizophrenic brain. Brain. Res. Rev. 31, 288-294. https://doi.org/10.1016/S0165-0173(99)00044-2
  27. Meshul, C. K., Bunker, G. L., Mason, J. N., Allen, C. and Janowsky. A. (1996) Effects of subchronic clozapine and haloperidol on striatal glutamatergic synapses. J. Neurochem. 67, 1965-1973. https://doi.org/10.1046/j.1471-4159.1996.67051965.x
  28. Tarazi, F. I., Florijn, W. J. and Creese, I. (1996) Regulation of ionotropic glutamate receptors following subchronic and chronic treatment with typical and atypical antipsychotics. Psychopharmacology 128, 371-379. https://doi.org/10.1007/s002130050147
  29. Giardino, L., Bortolotti, F., Orazzo, C., Pozza, M., Monteleone, P., Calza, L. and Maj, M. (1997) Effect of chronic clozapine administration on [3H]MK801-binding sites in the rat brain: a side-preference action in cortical areas. Brain Res. 762, 216-218. https://doi.org/10.1016/S0006-8993(97)00478-2
  30. McCoy, L., Cox, C. and Richfield, E. K. (1998) Antipsychotic drug regulation of AMPA receptor affinity states and GluR1, GluR2 splice variant expression. Synapse 28, 195-207. https://doi.org/10.1002/(SICI)1098-2396(199803)28:3<195::AID-SYN2>3.0.CO;2-5
  31. Spurney, C. F., Baca, S. M., Murray, A. M., Jaskiw, G. E., Kleinmann, J. E. and Hyde, T. M. (1999) Differential effects of haloperidol and clozapine on ionotropic glutamate receptors in rats. Synapse 34, 266-276. https://doi.org/10.1002/(SICI)1098-2396(19991215)34:4<266::AID-SYN3>3.0.CO;2-2
  32. Fitzgerald, L. W., Deutch, A. Y., Gasic, G., Heinemann, S. F. and Nestler, E. J. (1995) Regulation of cortical and subcortical glutamate receptor subunit expression by antipsychotic drugs. J. Neurosci. 15, 2453-2461.
  33. Riva, M. A., Tascedda, F., Lovati, E. and Racagni, G. (1997) Regulation of NMDA receptor subunit messenger RNA levels in the rat brain following acute and chronic exposure to antipsychotic drugs. Mol. Brain Res. 50, 136-142. https://doi.org/10.1016/S0169-328X(97)00175-7
  34. Healy, D. J. and Meador-Woodruff, J. H. (1997) Clozapine and haloperidol differentially affect AMPA and kainate receptor subunit mRNA levels in rat cortex and striatum. Mol. Brain Res. 47, 331-338. https://doi.org/10.1016/S0169-328X(97)00064-8
  35. Thony, B., Auerbach, G. and Blau, N. (2000) Tetrahydrobiopterin biosynthesis, regeneration and functions. Biochem. J. 347 Pt 1, 1-16. https://doi.org/10.1042/0264-6021:3470001
  36. Blau, N., Thony, B., Cotton, R. G. H. and Hyland, K. (2001) Disorders of tetrahydrobiopterin and related biogenic amines; in The metabolic and molecular bases of inherited disease. pp 1725-1776. McGraw-Hill, New York, USA.
  37. Park, Y. S., Heizmann, C. W., Wermuth, B., Levine, R. A., Steinerstauch, P., Guzman, J. and Blau, N. (1991) Human carbonyl and aldose reductases: new catalytic functions in tetrahydrobiopterin biosynthesis. Biochem. Biophys. Res. Commun. 175, 738-744. https://doi.org/10.1016/0006-291X(91)91628-P
  38. Kaufman, S. (1963) The structure of the phenylalaninehydroxylation cofactor. Proc. Natl. Acad. Sci. U.S.A. 50, 1085-1093. https://doi.org/10.1073/pnas.50.6.1085
  39. Levitt, M., Spector, S., Sjoerdsma, A. and Udenfriend, S. (1965) Elucidation of the rate-limiting step in norepinephrine biosynthesis in perfused guinea-pig heart. J. Pharmacol. Exp. Ther. 148, 1-8.
  40. Hosoda, S. and Glick, D. (1966) Studies in histochemistry. LXXIX. Properties of tryptophan hydroxylase from neoplastic murine mast cells. J. Biol. Chem. 241, 192-196.
  41. Kwon, N. S., Nathan, C. F. and Stuehr, D. J. (1989) Reduced biopterin as a cofactor in the generation of nitrogen oxides by murine macrophages. J. Biol. Chem. 264, 20496-20501.
  42. Tayeh, M. A. and Marletta, M. A. (1989) Macrophage oxidation of L-arginine to nitric oxide, nitrite, and nitrate. Tetrahydrobiopterin is required as a cofactor. J. Biol. Chem. 264, 19654-19658.
  43. Sumi-Ichinose, C., Urano, F., Kuroda, R., Ohye, T., Kojima, M., Tazawa, M., Shiraishi, H., Hagino, Y., Nagatsu, T., Nomura, T. and Ichinose, H. (2001) Catecholamines and serotonin are differently regulated by tetrahydrobiopterin. A study from 6-pyruvoyltetrahydropterin synthase knockout mice. J. Biol. Chem. 276, 41150-41160. https://doi.org/10.1074/jbc.M102237200
  44. Yang, S., Lee, Y. J., Kim, J. M., Park, S., Peris, J., Laipis, P., Park, Y. S., Chung, J. H. and Oh, S. P. (2006) A murine model for human sepiapterin-reductase deficiency. Am. J. Hum. Genet. 78, 575-587. https://doi.org/10.1086/501372
  45. Kuhn, D. M. and Geddes, T. J. (2003) Tetrahydrobiopterin prevents nitration of tyrosine hydroxylase by peroxynitrite and nitrogen dioxide. Mol. Pharmacol. 64, 946-953. https://doi.org/10.1124/mol.64.4.946
  46. Satoh, M., Fujimoto, S., Haruna, Y., Arakawa, S., Horike, H., Komai, N., Sasaki, T., Tsujioka, K., Makino, H. and Kashihara, N. (2005) NAD(P)H oxidase and uncoupled nitric oxide synthase are major sources of glomerular superoxide in rats with experimental diabetic nephropathy. Am. J. Physiol. Renal. Physiol. 288, F1144-1152. https://doi.org/10.1152/ajprenal.00221.2004
  47. Satoh, M., Fujimoto, S., Arakawa, S., Yada, T., Namikoshi, T., Haruna, Y., Horike, H., Sasaki, T. and Kashihara, N. (2008) Angiotensin II type 1 receptor blocker ameliorates uncoupled endothelial nitric oxide synthase in rats with experimental diabetic nephropathy. Nephrol. Dial. Transplant. 23, 3806-3813. https://doi.org/10.1093/ndt/gfn357
  48. Snyder, S. H. and Ferris, C. D. (2000) Novel neurotransmitters and their neuropsychiatric relevance. Am. J. Psychiatry 157, 1738-1751. https://doi.org/10.1176/appi.ajp.157.11.1738
  49. Brenman, J. E. and Bredt, D. S. (1997) Synaptic signaling by nitric oxide. Curr. Opin. Neurobiol. 7, 374-378. https://doi.org/10.1016/S0959-4388(97)80065-7
  50. Akyol, O., Zoroglu, S. S., Armutcu, F., Sahin, S. and Gurel, A. (2004) Nitric oxide as a physiopathological factor in neuropsychiatric disorders. In Vivo 18, 377-390.
  51. Kiss, J. P. (2000) Role of nitric oxide in the regulation of monoaminergic neurotransmission. Brain Res. Bull. 52, 459-466. https://doi.org/10.1016/S0361-9230(00)00282-3
  52. Mataga, N., Imamura, K. and Watanabe, Y. (1991) 6R-tetrahydrobiopterin perfusion enhances dopamine, serotonin, and glutamate outputs in dialysate from rat striatum and frontal cortex. Brain Res. 551, 64-71. https://doi.org/10.1016/0006-8993(91)90914-H
  53. Koshimura, K., Miwa, S., Lee, K., Fujiwara, M. and Watanabe, Y. (1990) Enhancement of dopamine release in vivo from the rat striatum by dialytic perfusion of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin. J. Neurochem. 54, 1391-1397. https://doi.org/10.1111/j.1471-4159.1990.tb01974.x
  54. Liang, L. P. and Kaufman, S. (1998) The regulation of dopamine release from striatum slices by tetrahydrobiopterin and L-arginine-derived nitric oxide. Brain Res. 800, 181-186. https://doi.org/10.1016/S0006-8993(98)00452-1
  55. Wolf, W. A., Ziaja, E., Arthur, R. A. Jr., Anastasiadis, P. Z., Levine, R. A. and Kuhn, D. M. (1991) Effect of tetrahydrobiopterin on serotonin synthesis, release, and metabolism in superfused hippocampal slices. J. Neurochem. 57, 1191-1197. https://doi.org/10.1111/j.1471-4159.1991.tb08279.x
  56. Fiege, B., Ballhausen, D., Kierat, L., Leimbacher, W., Goriounov, D., Schircks, B., Thony, B. and Blau. N. (2004) Plasma tetrahydrobiopterin and its pharmacokinetic following oral administration. Mol. Genet. Metab. 81, 45-51.
  57. Garbutt, J. C., van Kammen, D. P., Levine, R. A., Sternberg, D. E., Murphy, D. L., Ballenger, J., Bunney, W. E. Jr. and Lovenberg, W. M. (1982) Cerebrospinal fluid hydroxylase cofactor in schizophrenia. Psychiatry Res. 6, 145-151. https://doi.org/10.1016/0165-1781(82)90002-6
  58. Duch, D. S., Woolf, J. H., Nichol, C. A., Davidson, J. R. and Garbutt, J. C. (1984) Urinary excretion of biopterin and neopterin in psychiatric disorders. Psychiatry. Res. 11, 83-89. https://doi.org/10.1016/0165-1781(84)90090-8
  59. Leeming, R. J., Blair, J. A., Melikian, V. and O'Gorman, D. J. (1976) Biopterin derivatives in human body fluids and tissues. J. Clin. Pathol. 29, 444-451. https://doi.org/10.1136/jcp.29.5.444
  60. Richardson, M. A., Read, L. L., Taylor Clelland, C. L., Reilly, M. A., Chao, H. M., Guynn, R. W., Suckow, R. F. and Clelland, J. D. (2005) Evidence for a tetrahydrobiopterin deficit in schizophrenia. Neuropsychobiology 52, 190-201. https://doi.org/10.1159/000089002
  61. Richardson, M. A., Read, L. L., Reilly, M. A., Clelland, J. D. and Clelland, C. L. (2007) Analysis of plasma biopterin levels in psychiatric disorders suggests a common $BH_4$ deficit in schizophrenia and schizoaffective disorder. Neurochem. Res. 32, 107-113. https://doi.org/10.1007/s11064-006-9233-5
  62. Bjerkenstedt, L., Edman, G., Hagenfeldt, L., Sedvall, G. and Wiesel, F. A. (1985) Plasma amino acids in relation to cerebrospinal fluid monoamine metabolites in schizophrenic patients and healthy controls. Br. J. Psychiatry 147, 276-282. https://doi.org/10.1192/bjp.147.3.276
  63. Lindstrom, L. H. (1985) Low HVA and normal 5HIAA CSF levels in drug-free schizophrenic patients compared to healthy volunteers: correlations to symptomatology and family history. Psychiatry. Res. 14, 265-273. https://doi.org/10.1016/0165-1781(85)90095-2
  64. Gattaz, W. F., Waldmeier, P. and Beckmann, H. (1982) CSF monoamine metabolites in schizophrenic patients. Acta. Psychiatr. Scand. 66, 350-360. https://doi.org/10.1111/j.1600-0447.1982.tb06717.x
  65. Potkin, S. G., Weinberger, D. R., Linnoila, M. and Wyatt, R. J. (1983) Low CSF 5-hydroxyindoleacetic acid in schizophrenic patients with enlarged cerebral ventricles. Am. J. Psychiatry 140, 21-25. https://doi.org/10.1176/ajp.140.1.21
  66. Eells, J. B., Misler, J. A. and Nikodem, V. M. (2006) Reduced tyrosine hydroxylase and GTP cyclohydrolase mRNA expression, tyrosine hydroxylase activity, and associated neurochemical alterations in Nurr1-null heterozygous mice. Brain Res. Bull. 70, 186-195. https://doi.org/10.1016/j.brainresbull.2006.05.004
  67. Gil, M., McKinney, C., Lee, M. K., Eells, J. B., Phyillaier, M. A. and Nikodem, V. M. (2007) Regulation of GTP cyclohydrolase I expression by orphan receptor Nurr1 in cell culture and in vivo. J. Neurochem. 101, 142-150.
  68. Xing, G., Zhang, L., Russell, S. and Post, R. (2006) Reduction of dopamine-related transcription factors Nurr1 and NGFI-B in the prefrontal cortex in schizophrenia and bipolar disorders. Schizophr. Res. 84, 36-56. https://doi.org/10.1016/j.schres.2005.11.006
  69. Hitri, A., Hurd, Y. L., Wyatt, R. J. and Deutsch, S. I. (1994) Molecular, functional and biochemical characteristics of the dopamine transporter: regional differences and clinical relevance. Clin. Neuropharmacol. 17, 1-22. https://doi.org/10.1097/00002826-199402000-00001
  70. Giros, B., Jaber, M., Jones, S. R., Wightman, R. M. and Caron, M. G. (1996) Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter. Nature 379, 606-612. https://doi.org/10.1038/379606a0

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