Chapter 6: Role of tryptophan metabolism in mood, behavior, and cognition

Targeting the Broadly Pathogenic Kynurenine Pathway

Volumn , Issue , 2015, Pages 76-89

  Gostner, Johanna M ^a   Becker, Kathrin ^a   Sperner Unterweger, Barbara ^a   Überall, Florian ^a   Fuchs, Dietmar ^a   Strasser, Barbara ^a  

^a INNSBRUCK MEDICAL UNIVERSITY   (Austria)

Author keywords

3 dioxygenase; Antioxidants; Immune activation; Indoleamine 2; Infl ammation; Interferon ; Neopterin; Reactive oxygen species; Serotonin; Tryptophan; Vitamins

Indexed keywords

EID: 84943583540     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1007/978-3-319-11870-3_6     Document Type: Chapter

References (74)

1. Chen Y, Guillemin GJ. Kynurenine pathway metabolites in humans: disease and healthy states. Int J Tryptophan Res. 2009;2:1-19.
2. Widner B, Werner ER, Schennach H, Wachter H, Fuchs D. Simultaneous measurement of serum tryptophan and kynurenine by HPLC. Clin Chem. 1997;43:2424-6.
3. Werner ER, Bitterlich G, Fuchs D, Hausen A, Reibnegger G, Szabo G, et al. Human macrophages degrade tryptophan upon induction by interferon-gamma. Life Sci. 1987;41:273-80.
4. Werner-Felmayer G, Werner ER, Fuchs D, Hausen A, Reibnegger G, Wachter H. Tumour necrosis factor-alpha and lipopolysaccharide enhance interferon-induced tryptophan degradation and pteridine synthesis in human cells. Biol Chem Hoppe Seyler. 1989;370:1063-9.
5. Werner-Felmayer G, Werner ER, Fuchs D, Hausen A, Reibnegger G, Wachter H. Neopterin formation and tryptophan degradation by a human myelomonocytic cell line (THP-1). Cancer Res. 1990;50:2863-7.
6. Byrne GI, Lehmann LK, Kirschbaum JG, Borden EC, Lee CM, Brown RR. Induction of tryptophan degradation in vitro and in vivo: a gamma-interferon-stimulated activity. J Interferon Res. 1986;64:389-96.
7. Widner B, Sepp N, Kowald E, Ortner U, Wirleitner B, Fritsch P, et al. Enhanced tryptophan degradation in systemic lupus erythematosus. Immunobiology. 2000;201:621-30.
8. Weinlich G, Murr C, Richardsen L, Winkler C, Fuchs D. Decreased serum tryptophan concentration predicts poor prognosis in malignant melanoma patients. Dermatology. 2007; 214:8-14.
9. Giusti RM, Maloney EM, Hanchard B, Morgan OSC, Steinberg SM, Wachter H, et al. Differential patterns of serum biomarkers of immune activation in human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis and adult T-cell leukemia/lymphoma. Cancer Epidemiol Biomark Prev. 1996;5:699-709.
10. Schroecksnadel K, Wirleitner B, Winkler C, Fuchs D. Monitoring tryptophan metabolism in chronic immune activation. Clin Chim Acta. 2006;364:82-90.
11. Huang A, Fuchs D, Widner B, Glover C, Henderson DC, Allen-Mersh TG. Serum tryptophan decrease correlates with immune activation and impaired quality of life in colorectal cancer. Br J Cancer. 2002;86:1691-6.
12. Schröcksnadel H, Baier-Bitterlich G, Dapunt O, Wachter H, Fuchs D. Decreased plasma tryptophan in pregnancy. Obstet Gynecol. 1996;88:47-50.
13. Heyes MP, Saito K, Crowley JS, Davis LE, Demitrack MA, Der M, et al. Quinolinic acid and kynurenine pathway metabolism in inflammatory and non-inflammatory neurological disease. Brain. 1992;115:1249-73.
14. Theofylaktopoulou D, Ulvik A, Midttun O, Ueland PM, Vollset SE, Nygård O, et al. Vitamins B2 and B6 as determinants of kynurenines and related markers of interferon-γ-mediated immune activation in the community-based Hordaland Health Study. Br J Nutr. 2014;8:1-8.
15. Fuchs D, Jamnig H, Heininger P, Klieber M, Schroecksnadel S, Fiegl M, et al. Decline of exhaled isoprene in lung cancer patients correlates with immune activation. J Breath Res. 2012;6:027101.
16. Pfefferkorn ER. Interferon gamma blocks the growth of Toxoplasma gondii in human fibroblasts by inducing the host cells to degrade tryptophan. Proc Natl Acad Sci U S A. 1984; 81:908-12.
17. Werner-Felmayer G, Werner ER, Fuchs D, Hausen A, Reibnegger G, Wachter H. Characteristics of interferon induced tryptophan metabolism in human cells in vitro. Biochim Biophys Acta. 1989;1012:140-7.
18. Uyttenhove C, Pilotte L, Théate I, Stroobant V, Colau D, Parmentier N, et al. Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat Med. 2003;9:1269-74.
19. Fallarino F, Grohmann U, Vacca C, Bianchi R, Orabona C, Spreca A, et al. T cell apoptosis by tryptophan catabolism. Cell Death Differ. 2002;9:1069-77.
20. Trabanelli S, Ocadlikova D, Evangelisti C, Parisi S, Curti A. Induction of regulatory T Cells by dendritic cells through indoleamine 2,3-dioxygenase: a potent mechanism of acquired peripheral tolerance. Curr Med Chem. 2011;18:2234-9.
21. Widner B, Ledochowski M, Fuchs D. Interferon-gamma-induced tryptophan degradation: neuropsychiatric and immunological consequences. Curr Drug Metab. 2000;1:193-204.
22. Widner B, Laich A, Sperner-Unterweger B, Ledochowski M, Fuchs D. Neopterin production tryptophan degradation and mental depression: what is the link? Brain Behav Immun. 2002;16:590-5.
23. Capuron L, Dantzer R. Cytokines and depression: the need for a new paradigm. Brain Behav Immun. 2003;17 Suppl 1:S119-24.
24. Stone TW, Darlington LG. The kynurenine pathway as a therapeutic target in cognitive and neurodegenerative disorders. Br J Pharmacol. 2013;169:1211-27.
25. Botwinick IC, Pursell L, Yu G, Cooper T, Mann JJ, Chabot JA. A biological basis for depression in pancreatic cancer. HPB (Oxford). 2014;16:740-3.
26. Allison DJ, Ditor DS. The common inflammatory etiology of depression and cognitive impairment: a therapeutic target. J Neuroinflammation. 2014;11:151.
27. Capuron L, Neurauter G, Musselman DL, Lawson DH, Nemeroff CB, Fuchs D, et al. Interferon- alpha-induced changes in tryptophan metabolism. Relationship to depression and paroxetine treatment. Biol Psychiatry. 2003;54:906-14.
28. Capuron L, Schroecksnadel S, Féart C, Aubert A, Higueret D, Barberger-Gateau P, et al. Chronic low grade immune activation in the elderly is associated with increased tryptophan catabolism and altered phenylalanine turnover: role in neuropsychiatric symptomatology. Biol Psychiatry. 2011;70:175-82.
29. Oxenkrug GF. Metabolic syndrome, age-associated neuroendocrine disorders, and dysregulation of tryptophan-kynurenine metabolism. Ann N Y Acad Sci. 2010;1199:1-14.
30. Capuron L, Geisler S, Kurz K, Leblhuber F, Sperner-Unterweger B, Fuchs D. Activated immune system and inflammation in healthy ageing: relevance for tryptophan and neopterin metabolism. Curr Pharm Des (in press).
31. Sublette ME, Galfalvy HC, Fuchs D, Lapidus M, Grunebaum MF, Oquendo MA, et al. Plasma kynurenine levels are elevated in suicide attempters with major depressive disorder. Brain Behav Immun. 2011;25(6):1272-8.
32. O'Connor JC, Lawson MA, André C, Briley EM, Szegedi SS, Lestage J, et al. Induction of IDO by Bacille Calmette-Guérin is responsible for development of murine depressive-like behavior. J Immunol. 2009;182:3202-12.
33. Myint AM. Kynurenines: from the perspective of major psychiatric disorders. FEBS J. 2012;279(8):1375-85.
34. McGee E, Shevlin M. Effect of humor on interpersonal attraction and mate selection. J Psychol. 2009;143:67-77.
35. Wirleitner B, Reider D, Ebner S, Böck G, Widner B, Jaeger M, et al. Monocyte-derived dendritic cells release neopterin. J Leukoc Biol. 2002;72:1148-53.
36. Cano OD, Neurauter G, Fuchs D, Shearer GM, Boasso A. Differential effect of type I and type II interferons on neopterin production and amino acid metabolism in human astrocytes-derived cells. Neurosci Lett. 2008;438:22-5.
37. Schroecksnadel S, Sucher R, Kurz K, Fuchs D, Brandacher G. Influence of immunosuppressive agents on tryptophan degradation and neopterin production in human peripheral blood mononuclear cells. Transplant Immunol. 2011;25:119-23.
38. Schroecksnadel K, Winkler C, Wirleitner B, Schennach H, Fuchs D. Aspirin down-regulates tryptophan degradation in stimulated human peripheral blood mononuclear cells in vitro. Clin Exp Immunol. 2005;140:41-5.
39. Neurauter G, Wirleitner B, Laich A, Schennach H, Weiss G, Fuchs D. Atorvastatin suppresses interferon-γ-induced neopterin formation and tryptophan degradation in human peripheral blood mononuclear cells and in monocytic cell lines. Clin Exp Immunol. 2003;131:264-7.
40. Nathan CF, Murray HW, Wiebe ME, Rubin BY. Identification of interferon-gamma as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity. J Exp Med. 1983;158:670-89.
41. Schreck R, Rieber P, Baeuerle PA. Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-kappa B transcription factor and HIV-1. EMBO J. 1991;10:2247-58.
42. Schobersberger W, Hoffmann G, Grote J, Wachter H, Fuchs D. Induction of inducible nitric oxide synthase expression by neopterin in vascular smooth muscle cells. FEBS Lett. 1995;377:461-4.
43. Jenny M, Klieber M, Zaknun D, Schroecksnadel S, Kurz K, Ledochowski M, et al. In vitro testing for anti-inflammatory properties of compounds employing peripheral blood mononuclear cells freshly isolated from healthy donors. Inflamm Res. 2011;60:127-35.
44. Gostner J, Ciardi C, Becker K, Fuchs D, Sucher R. Immunoregulatory impact of food antioxidants. Curr Pharm Des. 2014;20:840-9.
45. Gostner JM, Schroecknsadel S, Jenny M, Klein A, Ueberall F, Schennach H, et al. Coffee extracts suppress tryptophan breakdown in mitogen-stimulated peripheral blood mononuclear cells. J Am Coll Nutr (in press).
46. Zaknun D, Schroecksnadel S, Kurz K, Fuchs D. Potential role of antioxidant food supplements, preservatives and colorants in the pathogenesis of allergy and asthma. Int Arch Allergy Immunol. 2012;157:113-24.
47. Winkler C, Schroecksnadel K, Schennach H, Fuchs D. Vitamin C and E suppress mitogenstimulated peripheral blood mononuclear cells in vitro. Int Arch Allergy Immunol. 2007;142:127-32.
48. Tan PH, Sagoo P, Chan C, Yates JB, Campbell J, Beutelspacher SC, et al. Inhibition of NF-kappa B and oxidative pathways in human dendritic cells by antioxidative vitamins generates regulatory T cells. J Immunol. 2005;174:7633-44.
49. Murr C, Winklhofer-Roob BM, Schroecksnadel K, Maritschnegg M, Mangge H, Böhm BO, et al. Inverse association between serum concentrations of neopterin and antioxidants in patients with and without angiographic coronary artery disease. Atherosclerosis. 2009;202:543-9.
50. Hulsken S, Märtin A, Mohajeri MH, Homberg JR. Food-derived serotonergic modulators: effects on mood and cognition. Nutr Res Rev. 2013;26:223-34.
51. Gómez-Pinilla F. Brain foods: the effects of nutrients on brain function. Nat Rev Neurosci. 2008;9:568-78.
52. Grosso G, Galvano F, Marventano S, Malaguarnera M, Bucolo C, Drago F, et al. Omega-3 fatty acids and depression: scientific evidence and biological mechanisms. Oxidative Med Cell Longev. 2014;2014:313570.
53. Sánchez-Villegas A, Martínez-González MA, Estruch R, Salas-Salvadó J, Corella D, Covas MI, et al. Mediterranean dietary pattern and depression: the PREDIMED randomized trial. BMC Med. 2013;11:208.
54. Jenny M, Santer E, Klein A, Ledochowski M, Schennach H, Ueberall F, et al. Cacao extracts suppress tryptophan degradation of mitogen-stimulated peripheral blood mononuclear cells. J Ethnopharmacol. 2009;207:75-82.
55. Gea A, Beunza JJ, Estruch R, Sánchez-Villegas A, Salas-Salvadó J, Buil-Cosiales P, et al. Alcohol intake, wine consumption and the development of depression: the PREDIMED study. BMC Med. 2013;11:192.
56. Gleissenthall GV, Geisler S, Malik P, Kemmler G, Benicke H, Fuchs D, et al. Tryptophan metabolism in post-withdrawal alcohol-dependent patients. Alcohol Alcohol. 2014;49:251-5.
57. Mougiakakos D, Jitschin R, Johansson CC, Okita R, Kiessling R, Le Blanc K. The impact of inflammatory licensing on heme oxygenase-1-mediated induction of regulatory T cells by human mesenchymal stem cells. Blood. 2011;117:4826-35.
58. Ryter SW, Choi AM. Heme oxygenase-1/carbon monoxide: novel therapeutic strategies in critical care medicine. Curr Drug Targets. 2010;11:1485-94.
59. Walter RB, Fuchs D, Weiss G, Walter TR, Reinhard WH. HMG-CoA reductase inhibitors are associated with decreased serum neopterin levels in stable coronary artery disease. Clin Chem Lab Med. 2003;41:1314-19.
60. Pedersen ER, Midttun Ø, Ueland PM, Schartum-Hansen H, Seifert R, Igland J, et al. Systemic markers of interferon-g-mediated immune activation and long-term prognosis in 2380 patients with stable coronary artery disease. Arterioscler Thromb Vasc Biol. 2011;31:698-704.
61. Fernstrom JD, Wurtman RJ. Brain serotonin content: increase following ingestion of carbohydrate diet. Science. 1971;174:1023-5.
62. Liverant GI, Sloan DM, Pizzagalli DA, Harte CB, Kamholz BW, Rosebrock LE, et al. Associations among smoking, anhedonia, and reward learning in depression. Behav Ther. 2014;45:651-63.
63. Komiyama M, Wada H, Ura S, Yamakage H, Satoh-Asahara N, Shimatsu A, et al. Analysis of factors that determine weight gain during smoking cessation therapy. PLoS One. 2013;8(8), e72010.
64. Farr OM, Tsoukas MA, Mantzoros CS. Leptin and the brain: influences on brain development, cognitive functioning and psychiatric disorders. Metabolism. 2014, pii: S0026- 0495(14)00199-1.
65. Ciardi C, Jenny M, Tschoner A, Überall F, Patsch J, Pedrini M, et al. Food additives sodium sulfite, sodium benzoate and curcumin inhibit leptin release in lipopolysaccharide-treated murine adipocytes in vitro. Br J Nutr. 2012;107:826-33.
66. Aggarwal BB, Shishodia S. Suppression of the nuclear factor-kappaB activation pathway by spice-derived phytochemicals: reasoning for seasoning. Ann N Y Acad Sci. 2004; 1030:434-41.
67. Mangge H, Summers KL, Meinitzer A, Zelzer S, Almer G, Prassl R, et al. Obesity-related dysregulation of the tryptophan-kynurenine metabolism: role of age and parameters of the metabolic syndrome. Obesity (Silver Spring). 2014;22:195-201.
68. Lee H, Ohno M, Ohta S, Mikami T. Regular moderate or intense exercise prevents depressionlike behavior without change of hippocampal tryptophan content in chronically tryptophandefi cient and stressed mice. PLoS One. 2013;8, e66996.
69. Melancon MO, Lorrain D, Dionne IJ. Changes in markers of brain serotonin activity in response to chronic exercise in senior men. Appl Physiol Nutr Metab. 2014;23:1-7.
70. Strasser B, Berger K, Fuchs D. Effects of a caloric restriction weight loss diet on tryptophan metabolism and inflammatory biomarkers in overweight adults. Eur J Nutr (in press).
71. Steinert RE, Luscombe-Marsh ND, Little TJ, Standfield S, Otto B, Horowitz M, et al. Effects of intraduodenal infusion of l-tryptophan on ad libitum eating, antropyloroduodenal motility, glycemia, insulinemia, and gut peptide secretion in healthy men. J Clin Endocrinol Metab. 2014;99:3275-84.
72. Neurauter G, Schröcksnadel K, Scholl-Bürgi S, Sperner-Unterweger B, Schubert C, Ledochowski M, et al. Chronic immune stimulation correlates with reduced phenylalanine turn-over. Curr Drug Metab. 2008;9:622-7.
73. Haroon E, Raison CL, Miller AH. Psychoneuroimmunology meets neuropsychopharmacology: translational implications of the impact of inflammation on behavior. Neuropsychopharmacology. 2012;37:137-62.
74. Fuchs D, Murr C, Reibnegger G, Weiss G, Werner ER, Werner-Felmayer G, et al. Nitric oxide synthase and antimicrobial armature of human macrophages. J Infect Dis. 1994;169:224.