A dialogue between the immune system and brain, spoken in the language of serotonin

ACS Chemical Neuroscience

Volumn 4, Issue 1, 2013, Pages 48-63

  Baganz, Nicole L ^a   Blakely, Randy D ^a,b  

^a VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b VANDERBILT UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

depression; immune system; interleukin 1 beta; P38 MAPK; Serotonin; serotonin transporter

Indexed keywords

CYTOKINE; MITOGEN ACTIVATED PROTEIN KINASE P38; SEROTONIN; SEROTONIN UPTAKE INHIBITOR;

ADAPTIVE IMMUNITY; ANXIETY DISORDER; AUTISM; BRAIN; CENTRAL NERVOUS SYSTEM; COGNITION; DEPRESSION; HUMAN; IMMUNE SYSTEM; IMMUNOMODULATION; INNATE IMMUNITY; NONHUMAN; OBSESSIVE COMPULSIVE DISORDER; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW;

ADAPTIVE IMMUNITY; ANIMALS; ANTIDEPRESSIVE AGENTS; BRAIN; CYTOKINES; HUMANS; IMMUNE SYSTEM; IMMUNITY, INNATE; MENTAL DISORDERS; MICE; MICE, KNOCKOUT; SEROTONIN; SEROTONIN PLASMA MEMBRANE TRANSPORT PROTEINS; SIGNAL TRANSDUCTION; SYNAPTIC TRANSMISSION;

EID: 84872511770     PISSN: None     EISSN: 19487193     Source Type: Journal    
DOI: 10.1021/cn300186b     Document Type: Review

References (237)

1. Canli, T. and Lesch, K. P. (2007) Long story short: the serotonin transporter in emotion regulation and social cognition Nat. Neurosci. 10, 1103-1109 (Pubitemid 47339957)
2. Passamonti, L., Crockett, M. J., Apergis-Schoute, A. M., Clark, L., Rowe, J. B., Calder, A. J., and Robbins, T. W. (2012) Effects of acute tryptophan depletion on prefrontal-amygdala connectivity while viewing facial signals of aggression Biol. Psychiatry 71, 36-43
3. van Erp, A. M. and Miczek, K. A. (2000) Aggressive behavior, increased accumbal dopamine, and decreased cortical serotonin in rats J. Neurosci. 20, 9320-9325 (Pubitemid 32042936)
4. Monti, J. M. (2011) Serotonin control of sleep-wake behavior Sleep Med. Rev. 15, 269-281
5. Blundell, J. E. (1984) Serotonin and appetite Neuropharmacology 23, 1537-1551 (Pubitemid 15152980)
6. Bardin, L. (2011) The complex role of serotonin and 5-HT receptors in chronic pain Behav. Pharmacol. 22, 390-404
7. Ducy, P. (2011) 5-HT and bone biology Curr. Opin. Pharmacol. 11, 34-38
8. Karsenty, G. and Yadav, V. K. (2011) Regulation of bone mass by serotonin: molecular biology and therapeutic implications Annu. Rev. Med. 62, 323-331
9. Lesurtel, M., Graf, R., Aleil, B., Walther, D. J., Tian, Y., Jochum, W., Gachet, C., Bader, M., and Clavien, P. A. (2006) Platelet-derived serotonin mediates liver regeneration Science 312, 104-107
10. White, J. G. (1970) A biphasic response of platelets to serotonin Scand. J. Haematol. 7, 145-151
11. Li, N., Wallen, N. H., Ladjevardi, M., and Hjemdahl, P. (1997) Effects of serotonin on platelet activation in whole blood Blood Coagulation Fibrinolysis 8, 517-523 (Pubitemid 28023394)
12. Lesurtel, M., Soll, C., Graf, R., and Clavien, P. A. (2008) Role of serotonin in the hepato-gastroIntestinal tract: an old molecule for new perspectives Cell. Mol. Life Sci. 65, 940-952 (Pubitemid 351651633)
13. Moore, R. Y., Halaris, A. E., and Jones, B. E. (1978) Serotonin neurons of the midbrain raphe: ascending projections J. Comp. Neurol. 180, 417-438
14. Bang, S. J., Jensen, P., Dymecki, S. M., and Commons, K. G. (2012) Projections and interconnections of genetically defined serotonin neurons in mice Eur. J. Neurosci. 35, 85-96
15. Lucki, I. (1998) The spectrum of behaviors influenced by serotonin Biol. Psychiatry 44, 151-162 (Pubitemid 28378297)
16. Caspi, A., Sugden, K., Moffitt, T. E., Taylor, A., Craig, I. W., Harrington, H., McClay, J., Mill, J., Martin, J., Braithwaite, A., and Poulton, R. (2003) Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene Science 301, 386-389 (Pubitemid 36877077)
17. Uher, R. and McGuffin, P. (2008) The moderation by the serotonin transporter gene of environmental adversity in the aetiology of mental illness: review and methodological analysis Mol. Psychiatry 13, 131-146
18. Blakely, R. D., Berson, H. E., Fremeau, R. T., Jr., Caron, M. G., Peek, M. M., Prince, H. K., and Bradley, C. C. (1991) Cloning and expression of a functional serotonin transporter from rat brain Nature 354, 66-70 (Pubitemid 21896784)
19. Fuller, R. W. and Wong, D. T. (1990) Serotonin uptake and serotonin uptake inhibition Ann. N.Y. Acad. Sci. 600, 68-78
20. Blakely, R. D., Ramamoorthy, S., Schroeter, S., Qian, Y., Apparsundaram, S., Galli, A., and DeFelice, L. J. (1998) Regulated phosphorylation and trafficking of antidepressant-sensitive serotonin transporter proteins Biol. Psychiatry 44, 169-178 (Pubitemid 28378299)
21. Ramamoorthy, S., Bauman, A. L., Moore, K. R., Han, H., Yang-Feng, T., Chang, A. S., Ganapathy, V., and Blakely, R. D. (1993) Antidepressant- and cocaine-sensitive human serotonin transporter: molecular cloning, expression, and chromosomal localization Proc. Natl. Acad. Sci. U.S.A. 90, 2542-2546 (Pubitemid 23078664)
22. Ramamoorthy, S. and Blakely, R. D. (1999) Phosphorylation and sequestration of serotonin transporters differentially modulated by psychostimulants Science 285, 763-766
23. Lotrich, F. E. and Pollock, B. G. (2004) Meta-analysis of serotonin transporter polymorphisms and affective disorders Psychiatr. Genet. 14, 121-129 (Pubitemid 39281818)
24. Lasky-Su, J. A., Faraone, S. V., Glatt, S. J., and Tsuang, M. T. (2005) Meta-analysis of the association between two polymorphisms in the serotonin transporter gene and affective disorders Am. J. Med. Genet., Part B 133, 110-115 (Pubitemid 40175627)
25. Schinka, J. A., Busch, R. M., and Robichaux-Keene, N. (2004) A meta-analysis of the association between the serotonin transporter gene polymorphism (5-HTTLPR) and trait anxiety Mol Psychiatry 9, 197-202 (Pubitemid 38299534)
26. McDougle, C. J., Epperson, C. N., Price, L. H., and Gelernter, J. (1998) Evidence for linkage disequilibrium between serotonin transporter protein gene (SLC6A4) and obsessive compulsive disorder Mol. Psychiatry 3, 270-273 (Pubitemid 28266338)
27. Lin, P. Y. (2007) Meta-analysis of the association of serotonin transporter gene polymorphism with obsessive-compulsive disorder Prog. Neuropsychopharmacol. Biol. Psychiatry 31, 683-689
28. Feinn, R., Nellissery, M., and Kranzler, H. R. (2005) Meta-analysis of the association of a functional serotonin transporter promoter polymorphism with alcohol dependence Am. J. Med. Genet., Part B 133B, 79-84 (Pubitemid 40175620)
29. Cook, E. H., Jr., Courchesne, R., Lord, C., Cox, N. J., Yan, S., Lincoln, A., Haas, R., Courchesne, E., and Leventhal, B. L. (1997) Evidence of linkage between the serotonin transporter and autistic disorder Mol Psychiatry 2, 247-250 (Pubitemid 27217689)
30. Mossner, R. and Lesch, K. P. (1998) Role of serotonin in the immune system and in neuroimmune interactions Brain Behav Immun 12, 249-271 (Pubitemid 29224829)
31. Ahern, G. P. (2011) 5-HT and the immune system Curr Opin Pharmacol 11, 29-33
32. Irwin, M. R. and Miller, A. H. (2007) Depressive disorders and immunity: 20 years of progress and discovery Brain, Behav., Immun. 21, 374-383 (Pubitemid 46528684)
33. Onore, C., Careaga, M., and Ashwood, P. (2012) The role of immune dysfunction in the pathophysiology of autism Brain, Behav., Immun. 26, 383-392
34. O'Connell, P. J., Wang, X., Leon-Ponte, M., Griffiths, C., Pingle, S. C., and Ahern, G. P. (2006) A novel form of immune signaling revealed by transmission of the inflammatory mediator serotonin between dendritic cells and T cells Blood 107, 1010-1017 (Pubitemid 43156299)
35. Csaba, G. and Kovacs, P. (2006) Perinuclear localization of biogenic amines (serotonin and histamine) in rat immune cells Cell Biol. Int. 30, 861-865 (Pubitemid 44635299)
36. Reddy, N. P. (1986) Lymph circulation: physiology, pharmacology, and biomechanics Crit. Rev. Biomed. Eng 14, 45-91
37. Zhu, C. B., Lindler, K. M., Owens, A. W., Daws, L. C., Blakely, R. D., and Hewlett, W. A. (2010) Interleukin-1 receptor activation by systemic lipopolysaccharide induces behavioral despair linked to MAPK regulation of CNS serotonin transporters Neuropsychopharmacology 35, 2510-2520
38. Parkin, J. and Cohen, B. (2001) An overview of the immune system Lancet 357, 1777-1789 (Pubitemid 32524226)
39. Ransohoff, R. M. and Brown, M. A. (2012) Innate immunity in the central nervous system J. Clin. Invest. 122, 1164-1171
40. Shapiro-Shelef, M. and Calame, K. (2005) Regulation of plasma-cell development Nat. Rev. Immunol. 5, 230-242 (Pubitemid 40364824)
41. Gershon, M. D. and Tack, J. (2007) The serotonin signaling system: from basic understanding to drug development for functional GI disorders Gastroenterology 132, 397-414 (Pubitemid 46127672)
42. Gershon, M. D., Drakontides, A. B., and Ross, L. L. (1965) Serotonin: Synthesis and Release from the Myenteric Plexus of the Mouse Intestine Science 149, 197-199
43. Kim, D. Y. and Camilleri, M. (2000) Serotonin: a mediator of the brain-gut connection Am. J. Gastroenterol. 95, 2698-2709
44. Rodriguez, M. J., Saura, J., Billett, E. E., Finch, C. C., and Mahy, N. (2001) Cellular localization of monoamine oxidase A and B in human tissues outside of the central nervous system Cell Tissue Res. 304, 215-220 (Pubitemid 32448987)
45. Finocchiaro, L. M., Arzt, E. S., Fernandez-Castelo, S., Criscuolo, M., Finkielman, S., and Nahmod, V. E. (1988) Serotonin and melatonin synthesis in peripheral blood mononuclear cells: stimulation by interferon-gamma as part of an immunomodulatory pathway J. Interferon Res. 8, 705-716 (Pubitemid 19042691)
46. Kushnir-Sukhov, N. M., Brown, J. M., Wu, Y., Kirshenbaum, A., and Metcalfe, D. D. (2007) Human mast cells are capable of serotonin synthesis and release J. Allergy Clin. Immunol. 119, 498-499 (Pubitemid 46204791)
47. Leon-Ponte, M., Ahern, G. P., and O'Connell, P. J. (2007) Serotonin provides an accessory signal to enhance T-cell activation by signaling through the 5-HT7 receptor Blood 109, 3139-3146 (Pubitemid 46572497)
48. Cohen, R. A. (1985) Platelet-induced neurogenic coronary contractions due to accumulation of the false neurotransmitter, 5-hydroxytryptamine J. Clin. Invest. 75, 286-292 (Pubitemid 15163996)
49. Cohen, R. A., Zitnay, K. M., and Weisbrod, R. M. (1987) Accumulation of 5-hydroxytryptamine leads to dysfunction of adrenergic nerves in canine coronary artery following intimal damage in vivo Circ. Res. 61, 829-833 (Pubitemid 18004578)
50. Thoa, N. B., Eccleston, D., and Axelrod, J. (1969) The accumulation of C14-serotonin in the guinea-pig vas deferens J. Pharmacol. Exp. Ther. 169, 68-73
51. Verbeuren, T. J., Jordaens, F. H., and Herman, A. G. (1983) Accumulation and release of [3H]-5-hydroxytryptamine in saphenous veins and cerebral arteries of the dog J. Pharmacol. Exp. Ther. 226, 579-588 (Pubitemid 13041540)
52. Kawasaki, H. and Takasaki, K. (1984) Vasoconstrictor response induced by 5-hydroxytryptamine released from vascular adrenergic nerves by periarterial nerve stimulation J. Pharmacol. Exp. Ther. 229, 816-822 (Pubitemid 14076416)
53. Saito, A. and Lee, T. J. (1987) Serotonin as an alternative transmitter in sympathetic nerves of large cerebral arteries of the rabbit Circ. Res. 60, 220-228 (Pubitemid 17078836)
54. Schroeter, S., Levey, A. I., and Blakely, R. D. (1997) Polarized expression of the antidepressant-sensitive serotonin transporter in epinephrine-synthesizing chromaffin cells of the rat adrenal gland Mol. Cell. Neurosci. 9, 170-184 (Pubitemid 27323430)
55. Holzwarth, M. A. and Brownfield, M. S. (1985) Serotonin coexists with epinephrine in rat adrenal medullary cells Neuroendocrinology 41, 230-236 (Pubitemid 15015227)
56. Verhofstad, A. A. J. and Jonsson, G. (1983) Immunohistochemical and neurochemical evidence for the presence of serotonin in the adrenal medulla of the rat Neuroscience 10 (4) 1443-1453 (Pubitemid 14178586)
57. Jackson, J. C., Walker, R. F., Brooks, W. H., and Roszman, T. L. (1988) Specific uptake of serotonin by murine macrophages Life Sci. 42, 1641-1650
58. Rudd, M. L., Nicolas, A. N., Brown, B. L., Fischer-Stenger, K., and Stewart, J. K. (2005) Peritoneal macrophages express the serotonin transporter J. Neuroimmunol. 159, 113-118 (Pubitemid 40126183)
59. Hoffman, B. J., Mezey, E., and Brownstein, M. J. (1991) Cloning of a serotonin transporter affected by antidepressants Science 254, 579-580 (Pubitemid 21917380)
60. Tamir, H., Theoharides, T. C., Gershon, M. D., and Askenase, P. W. (1982) Serotonin storage pools in basophil leukemia and mast cells: characterization of two types of serotonin binding protein and radioautographic analysis of the intracellular distribution of [3H]serotonin J. Cell Biol. 93, 638-647
61. Gordon, J. and Barnes, N. M. (2003) Lymphocytes transport serotonin and dopamine: agony or ecstasy? Trends Immunol. 24, 438-443 (Pubitemid 36928101)
62. Pfeiffer, J. R., Seagrave, J. C., Davis, B. H., Deanin, G. G., and Oliver, J. M. (1985) Membrane and cytoskeletal changes associated with IgE-mediated serotonin release from rat basophilic leukemia cells J. Cell Biol. 101, 2145-2155 (Pubitemid 16169944)
63. Konig, B., Bergmann, U., and Konig, W. (1992) Induction of inflammatory mediator release (serotonin and 12-hydroxyeicosatetraenoic acid) from human platelets by Pseudomonas aeruginosa glycolipid Infect. Immun. 60, 3150-3155
64. Boehme, S. A., Lio, F. M., Sikora, L., Pandit, T. S., Lavrador, K., Rao, S. P., and Sriramarao, P. (2004) Cutting edge: serotonin is a chemotactic factor for eosinophils and functions additively with eotaxin J. Immunol. 173, 3599-3603 (Pubitemid 39280718)
65. Muller, T., Durk, T., Blumenthal, B., Grimm, M., Cicko, S., Panther, E., Sorichter, S., Herouy, Y., Di Virgilio, F., Ferrari, D., Norgauer, J., and Idzko, M. (2009) 5-hydroxytryptamine modulates migration, cytokine and chemokine release and T-cell priming capacity of dendritic cells in vitro and in vivo PLoS One 4, e6453
66. Kushnir-Sukhov, N. M., Gilfillan, A. M., Coleman, J. W., Brown, J. M., Bruening, S., Toth, M., and Metcalfe, D. D. (2006) 5-hydroxytryptamine induces mast cell adhesion and migration J. Immunol. 177, 6422-6432 (Pubitemid 44628861)
67. Hellstrand, K. and Hermodsson, S. (1990) Enhancement of human natural killer cell cytotoxicity by serotonin: role of non-T/CD16+ NK cells, accessory monocytes, and 5-HT1A receptors Cell. Immunol. 127, 199-214 (Pubitemid 20119676)
68. Freire-Garabal, M., Nunez, M. J., Balboa, J., Lopez-Delgado, P., Gallego, R., Garcia-Caballero, T., Fernandez-Roel, M. D., Brenlla, J., and Rey-Mendez, M. (2003) Serotonin upregulates the activity of phagocytosis through 5-HT1A receptors Br. J. Pharmacol. 139, 457-463 (Pubitemid 36760378)
69. Hellstrand, K. and Hermodsson, S. (1987) Role of serotonin in the regulation of human natural killer cell cytotoxicity J. Immunol. 139, 869-875 (Pubitemid 17107090)
70. Dantzer, R., O'Connor, J. C., Freund, G. G., Johnson, R. W., and Kelley, K. W. (2008) From inflammation to sickness and depression: when the immune system subjugates the brain Nat. Rev. Neurosci. 9, 46-56 (Pubitemid 350295688)
71. Hellstrand, K., Czerkinsky, C., Ricksten, A., Jansson, B., Asea, A., Kylefjord, H., and Hermodsson, S. (1993) Role of serotonin in the regulation of interferon-gamma production by human natural killer cells J. Interferon Res. 13, 33-38 (Pubitemid 23078363)
72. Idzko, M., Panther, E., Stratz, C., Muller, T., Bayer, H., Zissel, G., Durk, T., Sorichter, S., Di Virgilio, F., Geissler, M., Fiebich, B., Herouy, Y., Elsner, P., Norgauer, J., and Ferrari, D. (2004) The serotoninergic receptors of human dendritic cells: identification and coupling to cytokine release J. Immunol. 172, 6011-6019 (Pubitemid 38621202)
73. Kelly, R. W., Carr, G. G., and Critchley, H. O. (1997) A cytokine switch induced by human seminal plasma: an immune modulation with implications for sexually transmitted disease Hum. Reprod. 12, 677-681 (Pubitemid 27223028)
74. Wilcox, B. D., Dumin, J. A., and Jeffrey, J. J. (1994) Serotonin regulation of interleukin-1 messenger RNA in rat uterine smooth muscle cells. Relationship to the production of interstitial collagenase J. Biol. Chem. 269, 29658-29664
75. Pousset, F., Fournier, J., Legoux, P., Keane, P., Shire, D., and Soubrie, P. (1996) Effect of serotonin on cytokine mRNA expression in rat hippocampal astrocytes Brain Res. 38, 54-62 (Pubitemid 26159192)
76. Babcock, T. A. and Carlin, J. M. (2000) Transcriptional activation of indoleamine dioxygenase by interleukin 1 and tumor necrosis factor alpha in interferon-treated epithelial cells Cytokine 12, 588-594 (Pubitemid 30453486)
77. Guillemin, G. J., Kerr, S. J., Pemberton, L. A., Smith, D. G., Smythe, G. A., Armati, P. J., and Brew, B. J. (2001) IFN-beta1b induces kynurenine pathway metabolism in human macrophages: potential implications for multiple sclerosis treatment J. Interferon Cytokine Res. 21, 1097-1101 (Pubitemid 34114289)
78. Sakash, J. B., Byrne, G. I., Lichtman, A., and Libby, P. (2002) Cytokines induce indoleamine 2,3-dioxygenase expression in human atheroma-asociated cells: implications for persistent Chlamydophila pneumoniae infection Infect. Immun. 70, 3959-3961 (Pubitemid 34666040)
79. Dang, Y., Dale, W. E., and Brown, O. R. (2000) Comparative effects of oxygen on indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase of the kynurenine pathway Free. Radical Biol. Med. 28, 615-624 (Pubitemid 30136043)
80. Dantzer, R., O'Connor, J. C., Lawson, M. A., and Kelley, K. W. (2011) Inflammation-associated depression: from serotonin to kynurenine Psychoneuroendocrinology 36, 426-436
81. Kim, H., Chen, L., Lim, G., Sung, B., Wang, S., McCabe, M. F., Rusanescu, G., Yang, L., Tian, Y., and Mao, J. (2012) Brain indoleamine 2,3-dioxygenase contributes to the comorbidity of pain and depression J. Clin. Invest. 122, 2940-2954
82. Marazziti, D., Consoli, G., Masala, I., Catena Dell'Osso, M., and Baroni, S. (2010) Latest advancements on serotonin and dopamine transporters in lymphocytes Mini Rev. Med. Chem. 10, 32-40
83. Lesch, K. P., Bengel, D., Heils, A., Sabol, S. Z., Greenberg, B. D., Petri, S., Benjamin, J., Muller, C. R., Hamer, D. H., and Murphy, D. L. (1996) Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region Science 274, 1527-1531 (Pubitemid 26403928)
84. Meredith, E. J., Chamba, A., Holder, M. J., Barnes, N. M., and Gordon, J. (2005) Close encounters of the monoamine kind: immune cells betray their nervous disposition Immunology 115, 289-295 (Pubitemid 40896027)
85. Buttarelli, F. R., Fanciulli, A., Pellicano, C., and Pontieri, F. E. (2011) The dopaminergic system in peripheral blood lymphocytes: from physiology to pharmacology and potential applications to neuropsychiatric disorders Curr. Neuropharmacol. 9, 278-288
86. Amenta, F., Bronzetti, E., Cantalamessa, F., El-Assouad, D., Felici, L., Ricci, A., and Tayebati, S. K. (2001) Identification of dopamine plasma membrane and vesicular transporters in human peripheral blood lymphocytes J. Neuroimmunol. 117, 133-142 (Pubitemid 32595500)
87. Marazziti, D., Baroni, S., Catena Dell'Osso, M., Masala, I., Fabbrini, L., Betti, L., Giannaccini, G., Dell'osso, B., and Lucacchini, A. (2008) Presence and characterization of the dopamine transporter in human resting lymphocytes Neurochem. Res. 33, 1011-1016
88. Stamford, J. A., Kruk, Z. L., and Millar, J. (1990) Striatal dopamine terminals release serotonin after 5-HTP pretreatment: in vivo voltammetric data Brain Res. 515, 173-180 (Pubitemid 20176112)
89. Jackson, B. P. and Wightman, R. M. (1995) Dynamics of 5-hydroxytryptamine released from dopamine neurons in the caudate putamen of the rat Brain Res. 674, 163-166
90. Kut, J. L., Young, M. R., Crayton, J. W., Wright, M. A., and Young, M. E. (1992) Regulation of murine T-lymphocyte function by spleen cell-derived and exogenous serotonin Immunopharmacol. Immunotoxicol. 14, 783-796 (Pubitemid 23000952)
91. Aune, T. M., Kelley, K. A., Ranges, G. E., and Bombara, M. P. (1990) Serotonin-activated signal transduction via serotonin receptors on Jurkat cells J. Immunol. 145, 1826-1831 (Pubitemid 20336750)
92. Aune, T. M., Golden, H. W., and McGrath, K. M. (1994) Inhibitors of serotonin synthesis and antagonists of serotonin 1A receptors inhibit T lymphocyte function in vitro and cell-mediated immunity in vivo J. Immunol. 153, 489-498 (Pubitemid 24206278)
93. Crews, F. T., Bechara, R., Brown, L. A., Guidot, D. M., Mandrekar, P., Oak, S., Qin, L., Szabo, G., Wheeler, M., and Zou, J. (2006) Cytokines and alcohol Alcohol.: Clin. Exp. Res. 30, 720-730
94. Matsumura, Y., Byrne, S. N., Nghiem, D. X., Miyahara, Y., and Ullrich, S. E. (2006) A role for inflammatory mediators in the induction of immunoregulatory B cells J. Immunol. 177, 4810-4817 (Pubitemid 44469816)
95. Meredith, E. J., Holder, M. J., Chamba, A., Challa, A., Drake Lee, A., Bunce, C. M., Drayson, M. T., Pilkington, G., Blakely, R. D., Dyer, M. J., Barnes, N. M., and Gordon, J. (2005) The serotonin transporter (SLC6A4) is present in B-cell clones of diverse malignant origin: probing a potential antitumor target for psychotropics FASEB J. 19, 1187-1189 (Pubitemid 40946460)
96. Anthony, I. C., Crawford, D. H., and Bell, J. E. (2003) B lymphocytes in the normal brain: contrasts with HIV-associated lymphoid infiltrates and lymphomas Brain 126, 1058-1067 (Pubitemid 36522949)
97. Pryce, G., Santos, W., and Male, D. (1994) An assay for the analysis of lymphocyte migration across cerebral endothelium in vitro J. Immunol. Methods 167, 55-63 (Pubitemid 24053772)
98. Hickey, W. F., Hsu, B. L., and Kimura, H. (1991) T-lymphocyte entry into the central nervous system J. Neurosci. Res. 28, 254-260
99. Walther, D. J., Peter, J. U., Winter, S., Holtje, M., Paulmann, N., Grohmann, M., Vowinckel, J., Alamo-Bethencourt, V., Wilhelm, C. S., Ahnert-Hilger, G., and Bader, M. (2003) Serotonylation of small GTPases is a signal transduction pathway that triggers platelet alpha-granule release Cell 115, 851-862 (Pubitemid 38058497)
100. Serafeim, A., Grafton, G., Chamba, A., Gregory, C. D., Blakely, R. D., Bowery, N. G., Barnes, N. M., and Gordon, J. (2002) 5-Hydroxytryptamine drives apoptosis in biopsylike Burkitt lymphoma cells: reversal by selective serotonin reuptake inhibitors Blood 99, 2545-2553 (Pubitemid 34525444)
101. Schneider, E., Machavoine, F., Bricard-Rignault, R., Levasseur, M., Petit-Bertron, A. F., Gautron, S., Ribeil, J. A., Launay, J. M., Mecheri, S., Cote, F., and Dy, M. (2011) Downregulation of basophil-derived IL-4 and in vivo T(H)2 IgE responses by serotonin and other organic cation transporter 3 ligands J. Allergy Clin. Immunol. 128, 864-871; e862.
102. Hellstrand, K. and Hermodsson, S. (1993) Serotonergic 5-HT1A receptors regulate a cell contact-mediated interaction between natural killer cells and monocytes Scand. J. Immunol. 37, 7-18 (Pubitemid 23020895)
103. Young, M. R., Kut, J. L., Coogan, M. P., Wright, M. A., Young, M. E., and Matthews, J. (1993) Stimulation of splenic T-lymphocyte function by endogenous serotonin and by low-dose exogenous serotonin Immunology 80, 395-400 (Pubitemid 23336688)
104. Young, M. R. and Matthews, J. P. (1995) Serotonin regulation of T-cell subpopulations and of macrophage accessory function Immunology 84, 148-152
105. Katoh, N., Soga, F., Nara, T., Tamagawa-Mineoka, R., Nin, M., Kotani, H., Masuda, K., and Kishimoto, S. (2006) Effect of serotonin on the differentiation of human monocytes into dendritic cells Clin. Exp. Immunol. 146, 354-361 (Pubitemid 44581352)
106. Dumery, L., Bourdel, F., Soussan, Y., Fialkowsky, A., Viale, S., Nicolas, P., and Reboud-Ravaux, M. (2001) beta-Amyloid protein aggregation: its implication in the physiopathology of Alzheimer's disease Pathol. Biol. 49, 72-85 (Pubitemid 32174334)
107. Martins, L. C., Rocha, N. P., Torres, K. C., Dos Santos, R. R., Franca, G. S., de Moraes, E. N., Mukhamedyarov, M. A., Zefirov, A. L., Rizvanov, A. A., Kiyasov, A. P., Vieira, L. B., Guimaraes, M. M., Yalvac, M. E., Teixeira, A. L., Bicalho, M. A., Janka, Z., Romano-Silva, M. A., Palotas, A., and Reis, H. J. (2012) Disease-specific expression of the serotonin-receptor 5-HT(2C) in natural killer cells in Alzheimer's dementia J. Neuroimmunol. 251, 73-79
108. Veenstra-VanderWeele, J. and Blakely, R. D. (2012) Networking in autism: leveraging genetic, biomarker and model system findings in the search for new treatments Neuropsychopharmacology 37, 196-212
109. Sutcliffe, J. S., Delahanty, R. J., Prasad, H. C., McCauley, J. L., Han, Q., Jiang, L., Li, C., Folstein, S. E., and Blakely, R. D. (2005) Allelic Heterogeneity at the Serotonin Transporter Locus (SLC6A4) Confers Susceptibility to Autism and Rigid-Compulsive Behaviors Am. J. Hum. Genet. 77, 265-279 (Pubitemid 41022709)
110. Veenstra-VanderWeele, J., Muller, C. L., Iwamoto, H., Sauer, J. E., Owens, W. A., Shah, C. R., Cohen, J., Mannangatti, P., Jessen, T., Thompson, B. J., Ye, R., Kerr, T. M., Carneiro, A. M., Crawley, J. N., Sanders-Bush, E., McMahon, D. G., Ramamoorthy, S., Daws, L. C., Sutcliffe, J. S., and Blakely, R. D. (2012) Autism gene variant causes hyperserotonemia, serotonin receptor hypersensitivity, social impairment and repetitive behavior Proc. Natl. Acad. Sci. U.S.A. 109, 5469-5474
111. Geschwind, D. H. (2009) Advances in autism Annu. Rev. Med. 60, 367-380
112. Hsiao, E. Y., McBride, S. W., Chow, J., Mazmanian, S. K., and Patterson, P. H. (2012) Modeling an autism risk factor in mice leads to permanent immune dysregulation Proc. Natl. Acad. Sci. U.S.A. 109, 12776-12781
113. Prasad, H. C., Hewlett, W. A., Sutcliffe, J. S., and Blakely, R. D. (2012) Immune System Dysregulation in Autism Linked to Hypperactivity of the Serotonin Transporter. Presented at the Biological Psychiatry Conference, Philadelphia, PA, May 3, 2012.
114. Carneiro, A. M., Airey, D. C., Thompson, B., Zhu, C. B., Lu, L., Chesler, E. J., Erikson, K. M., and Blakely, R. D. (2009) Functional coding variation in recombinant inbred mouse lines reveals multiple serotonin transporter- associated phenotypes Proc. Natl. Acad. Sci. U.S.A. 106, 2047-2052
115. Wong, M. L., Dong, C., Maestre-Mesa, J., and Licinio, J. (2008) Polymorphisms in inflammation-related genes are associated with susceptibility to major depression and antidepressant response Mol. Psychiatry 13, 800-812
116. Baune, B. T., Dannlowski, U., Domschke, K., Janssen, D. G., Jordan, M. A., Ohrmann, P., Bauer, J., Biros, E., Arolt, V., Kugel, H., Baxter, A. G., and Suslow, T. (2010) The interleukin 1 beta (IL1B) gene is associated with failure to achieve remission and impaired emotion processing in major depression Biol. Psychiatry 67, 543-549
117. Hwang, J. P., Tsai, S. J., Hong, C. J., Yang, C. H., Hsu, C. D., and Liou, Y. J. (2009) Interleukin-1 beta -511C/T genetic polymorphism is associated with age of onset of geriatric depression Neuromol. Med. 11, 322-327
118. Cerri, A. P., Arosio, B., Viazzoli, C., Confalonieri, R., Teruzzi, F., and Annoni, G. (2009) -308(G/A) TNF-alpha gene polymorphism and risk of depression late in the life Arch. Gerontol. Geriatr. 49 (Suppl 1) 29-34
119. Cerri, A. P., Arosio, B., Viazzoli, C., Confalonieri, R., Vergani, C., and Annoni, G. (2010) The -308 (G/A) single nucleotide polymorphism in the TNF-alpha gene and the risk of major depression in the elderly Int. J. Geriatr. Psychiatry 25, 219-223
120. Galecki, P., Florkowski, A., Bienkiewicz, M., and Szemraj, J. (2010) Functional polymorphism of cyclooxygenase-2 gene (G-765C) in depressive patients Neuropsychobiology 62, 116-120
121. Schiepers, O. J., Wichers, M. C., and Maes, M. (2005) Cytokines and major depression Prog. Neuropsychopharmacol. Biol. Psychiatry 29, 201-217 (Pubitemid 40202906)
122. Smith, R. S. (1991) The macrophage theory of depression Med. Hypotheses 35, 298-306
123. Capuron, L. and Ravaud, A. (1999) Prediction of the depressive effects of interferon alfa therapy by the patient's initial affective state N. Engl. J. Med. 340, 1370
124. Capuron, L., Ravaud, A., and Dantzer, R. (2000) Early depressive symptoms in cancer patients receiving interleukin 2 and/or interferon alfa-2b therapy J. Clin. Oncol. 18, 2143-2151 (Pubitemid 30324368)
125. Evans, D. L., Lynch, K. G., Benton, T., Dube, B., Gettes, D. R., Tustin, N. B., Lai, J. P., Metzger, D., and Douglas, S. D. (2008) Selective serotonin reuptake inhibitor and substance P antagonist enhancement of natural killer cell innate immunity in human immunodeficiency virus/acquired immunodeficiency syndrome Biol. Psychiatry 63, 899-905 (Pubitemid 351458446)
126. Frank, M. G., Hendricks, S. E., Johnson, D. R., Wieseler, J. L., and Burke, W. J. (1999) Antidepressants augment natural killer cell activity: in vivo and in vitro Neuropsychobiology 39, 18-24 (Pubitemid 29037760)
127. Hernandez, M. E., Martinez-Fong, D., Perez-Tapia, M., Estrada-Garcia, I., Estrada-Parra, S., and Pavon, L. (2010) Evaluation of the effect of selective serotonin-reuptake inhibitors on lymphocyte subsets in patients with a major depressive disorder Eur Neuropsychopharmacol. 20, 88-95
128. Zhu, J., Mix, E., Olsson, T., and Link, H. (1995) Influence of ion channel modulation on in vitro interferon-gamma induced MHC class I and II expression on macrophages Immunopharmacol. Immunotoxicol. 17, 109-136
129. Horikawa, H., Kato, T. A., Mizoguchi, Y., Monji, A., Seki, Y., Ohkuri, T., Gotoh, L., Yonaha, M., Ueda, T., Hashioka, S., and Kanba, S. (2010) Inhibitory effects of SSRIs on IFN-gamma induced microglial activation through the regulation of intracellular calcium Prog. Neuropsychopharmacol. Biol. Psychiatry 34, 1306-1316
130. Hannestad, J., DellaGioia, N., and Bloch, M. (2011) The effect of antidepressant medication treatment on serum levels of inflammatory cytokines: a meta-analysis Neuropsychopharmacology 36, 2452-2459
131. Lima, L. and Urbina, M. (2002) Serotonin transporter modulation in blood lymphocytes from patients with major depression Cell. Mol. Neurobiol. 22, 797-804 (Pubitemid 36169225)
132. Thompson, B. J., Jessen, T., Henry, L. K., Field, J. R., Gamble, K. L., Gresch, P. J., Carneiro, A. M., Horton, R. E., Chisnell, P. J., Belova, Y., McMahon, D. G., Daws, L. C., and Blakely, R. D. (2011) Transgenic elimination of high-affinity antidepressant and cocaine sensitivity in the presynaptic serotonin transporter Proc. Natl. Acad. Sci. U.S.A. 108, 3785-3790
133. Maes, M. (2001) The immunoregulatory effects of antidepressants Hum. Psychopharmacol. 16, 95-103 (Pubitemid 32219729)
134. Sacre, S., Medghalchi, M., Gregory, B., Brennan, F., and Williams, R. (2010) Fluoxetine and citalopram exhibit potent antiinflammatory activity in human and murine models of rheumatoid arthritis and inhibit toll-like receptors Arthritis Rheum 62, 683-693
135. Tsao, C. W., Lin, Y. S., Chen, C. C., Bai, C. H., and Wu, S. R. (2006) Cytokines and serotonin transporter in patients with major depression Prog. Neuropsychopharmacol. Biol. Psychiatry 30, 899-905
136. Basterzi, A. D., Aydemir, C., Kisa, C., Aksaray, S., Tuzer, V., Yazici, K., and Goka, E. (2005) IL-6 levels decrease with SSRI treatment in patients with major depression Hum. Psychopharmacol. 20, 473-476 (Pubitemid 41489458)
137. O'Brien, S. M., Scully, P., Fitzgerald, P., Scott, L. V., and Dinan, T. G. (2007) Plasma cytokine profiles in depressed patients who fail to respond to selective serotonin reuptake inhibitor therapy J. Psychiatr. Res. 41, 326-331 (Pubitemid 44854992)
138. Tynan, R. J., Weidenhofer, J., Hinwood, M., Cairns, M. J., Day, T. A., and Walker, F. R. (2012) A comparative examination of the anti-inflammatory effects of SSRI and SNRI antidepressants on LPS stimulated microglia Brain Behav. Immun 26, 469-479
139. Warner-Schmidt, J. L., Vanover, K. E., Chen, E. Y., Marshall, J. J., and Greengard, P. (2011) Antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) are attenuated by antiinflammatory drugs in mice and humans Proc. Natl. Acad. Sci. U.S.A. 108, 9262-9267
140. Moon, H. Y., Kim, S. H., Yang, Y. R., Song, P., Yu, H. S., Park, H. G., Hwang, O., Lee-Kwon, W., Seo, J. K., Hwang, D., Choi, J. H., Bucala, R., Ryu, S. H., Kim, Y. S., and Suh, P. G. (2012) Macrophage migration inhibitory factor mediates the antidepressant actions of voluntary exercise Proc. Natl. Acad. Sci. U.S.A. 109, 13094-13099
141. Yu, Y. W., Chen, T. J., Hong, C. J., Chen, H. M., and Tsai, S. J. (2003) Association study of the interleukin-1 beta (C-511T) genetic polymorphism with major depressive disorder, associated symptomatology, and antidepressant response Neuropsychopharmacology 28, 1182-1185
142. Tadic, A., Rujescu, D., Muller, M. J., Kohnen, R., Stassen, H. H., Szegedi, A., and Dahmen, N. (2008) Association analysis between variants of the interleukin-1beta and the interleukin-1 receptor antagonist gene and antidepressant treatment response in major depression Neuropsychiatr. Dis. Treat. 4, 269-276 (Pubitemid 351460964)
143. Murphy, D. L. and Lesch, K. P. (2008) Targeting the murine serotonin transporter: insights into human neurobiology Nat. Rev. Neurosci. 9, 85-96 (Pubitemid 351164876)
144. Uher, R., Perroud, N., Ng, M. Y., Hauser, J., Henigsberg, N., Maier, W., Mors, O., Placentino, A., Rietschel, M., Souery, D., Zagar, T., Czerski, P. M., Jerman, B., Larsen, E. R., Schulze, T. G., Zobel, A., Cohen-Woods, S., Pirlo, K., Butler, A. W., Muglia, P., Barnes, M. R., Lathrop, M., Farmer, A., Breen, G., Aitchison, K. J., Craig, I., Lewis, C. M., and McGuffin, P. (2010) Genome-wide pharmacogenetics of antidepressant response in the GENDEP project Am. J. Psychiatry 167, 555-564
145. Cutler, J. A., Rush, A. J., McMahon, F. J., and Laje, G. (2012) Common genetic variation in the indoleamine-2,3-dioxygenase genes and antidepressant treatment outcome in major depressive disorder J. Psychopharmacol. 26, 360-367
146. Crona, D., Harral, J., Adnot, S., Eddahibi, S., and West, J. (2009) Gene expression in lungs of mice lacking the 5-hydroxytryptamine transporter gene BMC Pulm. Med. 9, 19
147. Bischoff, S. C., Mailer, R., Pabst, O., Weier, G., Sedlik, W., Li, Z., Chen, J. J., Murphy, D. L., and Gershon, M. D. (2009) Role of serotonin in intestinal inflammation: knockout of serotonin reuptake transporter exacerbates 2,4,6-trinitrobenzene sulfonic acid colitis in mice Am. J. Physiol.: Gastrointest. Liver Physiol. 296, G685-695
148. Hofstetter, H., Gold, R., and Hartung, H. P. (2009) Th17 Cells in MS and Experimental Autoimmune Encephalomyelitis Int. MS J. 16, 12-18
149. Li, N., Ghia, J. E., Wang, H., McClemens, J., Cote, F., Suehiro, Y., Mallet, J., and Khan, W. I. (2011) Serotonin activates dendritic cell function in the context of gut inflammation Am. J. Pathol. 178, 662-671
150. Singh, Y. S., Sawarynski, L. E., Michael, H. M., Ferrell, R. E., Murphey-Corb, M. A., Swain, G. M., Patel, B. A., and Andrews, A. M. (2010) Boron-Doped Diamond Microelectrodes Reveal Reduced Serotonin Uptake Rates in Lymphocytes from Adult Rhesus Monkeys Carrying the Short Allele of the 5-HTTLPR ACS Chem. Neurosci. 1, 49-64
151. Singh, Y. S., Altieri, S. C., Gilman, T. L., Michael, H. M., Tomlinson, I. D., Rosenthal, S. J., Swain, G. M., Murphey-Corb, M. A., Ferrell, R. E., and Andrews, A. M. (2012) Differential serotonin transport is linked to the rh5-HTTLPR in peripheral blood cells Transl. Psychiatry 2, e77
152. Carvalho, L. S., Correa, H., Silva, G. C., Campos, F. S., Baiao, F. R., Ribeiro, L. S., Faria, A. M., and d'Avila Reis, D. (2008) May genetic factors in fibromyalgia help to identify patients with differentially altered frequencies of immune cells? Clin. Exp. Immunol. 154, 346-352
153. Lima, L., Mata, S., and Urbina, M. (2005) Allelic isoforms and decrease in serotonin transporter mRNA in lymphocytes of patients with major depression Neuroimmunomodulation 12, 299-306 (Pubitemid 41318213)
154. Mossner, R., Daniel, S., Schmitt, A., Albert, D., and Lesch, K. P. (2001) Modulation of serotonin transporter function by interleukin-4 Life Sci. 68, 873-880 (Pubitemid 32168063)
155. Matsunaga, M., Murakami, H., Yamakawa, K., Isowa, T., Kasugai, K., Yoneda, M., Kaneko, H., Fukuyama, S., Shinoda, J., Yamada, J., and Ohira, H. (2010) Genetic variations in the serotonin transporter gene-linked polymorphic region influence attraction for a favorite person and the associated interactions between the central nervous and immune systems Neurosci. Lett. 468, 211-215
156. Dinarello, C. A. (1984) Interleukin-1 Rev. Infect. Dis. 6, 51-95
157. Loppnow, H., Libby, P., Freudenberg, M., Krauss, J. H., Weckesser, J., and Mayer, H. (1990) Cytokine induction by lipopolysaccharide (LPS) corresponds to lethal toxicity and is inhibited by nontoxic Rhodobacter capsulatus LPS Infect. Immun. 58, 3743-3750 (Pubitemid 20353378)
158. Dunn, M. J. and Killcross, S. (2006) Differential attenuation of d-amphetamine-induced disruption of conditional discrimination performance by dopamine and serotonin antagonists Psychopharmacology (Berlin, Ger.) 188, 183-192 (Pubitemid 44371156)
159. Qin, L., He, J., Hanes, R. N., Pluzarev, O., Hong, J. S., and Crews, F. T. (2008) Increased systemic and brain cytokine production and neuroinflammation by endotoxin following ethanol treatment J. Neuroinflammation 5, 10
160. Blatteis, C. M. (1990) Neuromodulative actions of cytokines Yale J. Biol. Med. 63, 133-146 (Pubitemid 20342083)
161. Persidsky, Y., Stins, M., Way, D., Witte, M. H., Weinand, M., Kim, K. S., Bock, P., Gendelman, H. E., and Fiala, M. (1997) A model for monocyte migration through the blood-brain barrier during HIV-1 encephalitis J. Immunol. 158, 3499-3510 (Pubitemid 127484072)
162. Banks, W. A., Kastin, A. J., and Broadwell, R. D. (1995) Passage of cytokines across the blood-brain barrier Neuroimmunomodulation 2, 241-248 (Pubitemid 26082188)
163. Mark, K. S. and Miller, D. W. (1999) Increased permeability of primary cultured brain microvessel endothelial cell monolayers following TNF-alpha exposure Life Sci. 64, 1941-1953 (Pubitemid 29215195)
164. Raub, T. J., Kuentzel, S. L., and Sawada, G. A. (1992) Permeability of bovine brain microvessel endothelial cells in vitro: barrier tightening by a factor released from astroglioma cells Exp. Cell Res. 199, 330-340
165. Kacimi, R., Giffard, R. G., and Yenari, M. A. (2011) Endotoxin-activated microglia injure brain derived endothelial cells via NF-kappaB, JAK-STAT and JNK stress kinase pathways J. Inflammation (London, U.K.) 8, 7
166. Quan, N., Whiteside, M., Kim, L., and Herkenham, M. (1997) Induction of inhibitory factor kappaBalpha mRNA in the central nervous system after peripheral lipopolysaccharide administration: an in situ hybridization histochemistry study in the rat Proc. Natl. Acad. Sci. U.S.A. 94, 10985-10990 (Pubitemid 27430847)
167. Herkenham, M., Lee, H. Y., and Baker, R. A. (1998) Temporal and spatial patterns of c-fos mRNA induced by intravenous interleukin-1: a cascade of non-neuronal cellular activation at the blood-brain barrier J. Comp. Neurol. 400, 175-196 (Pubitemid 28440742)
168. Banks, W. A. (2005) Blood-brain barrier transport of cytokines: a mechanism for neuropathology Curr. Pharm. Des. 11, 973-984 (Pubitemid 40331299)
169. Banks, W. A., Kastin, A. J., and Gutierrez, E. G. (1993) Interleukin-1 alpha in blood has direct access to cortical brain cells Neurosci. Lett. 163, 41-44
170. McLay, R. N., Kastin, A. J., and Zadina, J. E. (2000) Passage of interleukin-1-beta across the blood-brain barrier is reduced in aged mice: a possible mechanism for diminished fever in aging Neuroimmunomodulation 8, 148-153 (Pubitemid 32008826)
171. Magni, F., Bruschi, F., and Kasti, M. (1987) The afferent innervation of the thymus gland in the rat Brain Res. 424, 379-385 (Pubitemid 18047683)
172. Dunn, A. J. (1992) Endotoxin-induced activation of cerebral catecholamine and serotonin metabolism: comparison with interleukin-1 J. Pharmacol. Exp. Ther. 261, 964-969
173. Gutierrez, E. G., Banks, W. A., and Kastin, A. J. (1993) Murine tumor necrosis factor alpha is transported from blood to brain in the mouse J. Neuroimmunol. 47, 169-176 (Pubitemid 23284281)
174. Gutierrez, E. G., Banks, W. A., and Kastin, A. J. (1994) Blood-borne interleukin-1 receptor antagonist crosses the blood-brain barrier J. Neuroimmunol. 55, 153-160
175. Ma, X. C., Chen, L. T., Oliver, J., Horvath, E., and Phelps, C. P. (2000) Cytokine and adrenal axis responses to endotoxin Brain Res. 861, 135-142 (Pubitemid 30177291)
176. Ericsson, A., Kovacs, K. J., and Sawchenko, P. E. (1994) A functional anatomical analysis of central pathways subserving the effects of interleukin-1 on stress-related neuroendocrine neurons J. Neurosci. 14, 897-913 (Pubitemid 24043940)
177. Rosas-Ballina, M., Ochani, M., Parrish, W. R., Ochani, K., Harris, Y. T., Huston, J. M., Chavan, S., and Tracey, K. J. (2008) Splenic nerve is required for cholinergic antiinflammatory pathway control of TNF in endotoxemia Proc. Natl. Acad. Sci. U.S.A. 105, 11008-11013
178. Bulloch, K. and Pomerantz, W. (1984) Autonomic nervous system innervation of thymic-related lymphoid tissue in wildtype and nude mice J. Comp. Neurol. 228, 57-68 (Pubitemid 14061779)
179. Pospieszny, N. (1979) Distribution of the vagus nerve of the stomach and certain lymph nodes of the sheep in the prenatal period (author's transl) Anat. Anz. 146, 47-59 (Pubitemid 9233750)
180. Olofsson, P. S., Rosas-Ballina, M., Levine, Y. A., and Tracey, K. J. (2012) Rethinking inflammation: neural circuits in the regulation of immunity Immunol. Rev. 248, 188-204
181. Niijima, A., Hori, T., Katafuchi, T., and Ichijo, T. (1995) The effect of interleukin-1 beta on the efferent activity of the vagus nerve to the thymus J. Auton. Nerv. Syst. 54, 137-144
182. Goehler, L. E., Gaykema, R. P., Hammack, S. E., Maier, S. F., and Watkins, L. R. (1998) Interleukin-1 induces c-Fos immunoreactivity in primary afferent neurons of the vagus nerve Brain Res. 804, 306-310 (Pubitemid 28496634)
183. Ek, M., Kurosawa, M., Lundeberg, T., and Ericsson, A. (1998) Activation of vagal afferents after intravenous injection of interleukin-1beta: role of endogenous prostaglandins J. Neurosci. 18, 9471-9479 (Pubitemid 28512476)
184. Goehler, L. E., Gaykema, R. P., Nguyen, K. T., Lee, J. E., Tilders, F. J., Maier, S. F., and Watkins, L. R. (1999) Interleukin-1beta in immune cells of the abdominal vagus nerve: a link between the immune and nervous systems? J. Neurosci. 19, 2799-2806 (Pubitemid 29162426)
185. Roosevelt, R. W., Smith, D. C., Clough, R. W., Jensen, R. A., and Browning, R. A. (2006) Increased extracellular concentrations of norepinephrine in cortex and hippocampus following vagus nerve stimulation in the rat Brain Res. 1119, 124-132 (Pubitemid 44647233)
186. Wan, W., Wetmore, L., Sorensen, C. M., Greenberg, A. H., and Nance, D. M. (1994) Neural and biochemical mediators of endotoxin and stress-induced c-fos expression in the rat brain Brain Res. Bull. 34, 7-14 (Pubitemid 24099719)
187. Konsman, J. P., Luheshi, G. N., Bluthe, R. M., and Dantzer, R. (2000) The vagus nerve mediates behavioural depression, but not fever, in response to peripheral immune signals; a functional anatomical analysis Eur. J. Neurosci. 12, 4434-4446 (Pubitemid 32037852)
188. Romeo, H. E., Tio, D. L., and Taylor, A. N. (2003) Effects of glossopharyngeal nerve transection on central and peripheral cytokines and serum corticosterone induced by localized inflammation J. Neuroimmunol. 136, 104-111 (Pubitemid 36298849)
189. Brambilla, D., Francoisi, S., Opp, M. R., and Imeri, L. (2007) Interleukin-1 inhibits firing of serotonergic neurons in the dorsal raphe nucleus and enhances GABAergic inhibitory post-synaptic potentials Eur. J. Neurosci. 26, 1862-1869 (Pubitemid 47493185)
190. Merali, Z., Lacosta, S., and Anisman, H. (1997) Effects of interleukin-1beta and mild stress on alterations of norepinephrine, dopamine and serotonin neurotransmission: a regional microdialysis study Brain Res. 761, 225-235 (Pubitemid 27305981)
191. Shintani, F., Kanba, S., Nakaki, T., Nibuya, M., Kinoshita, N., Suzuki, E., Yagi, G., Kato, R., and Asai, M. (1993) Interleukin-1b a augments release of norepinephrine, dopamine, and serotonin in the rat anterior hypothalamus J. Neurosci. 13 (8) 3574-3581 (Pubitemid 23241191)
192. Linthorst, A. C., Flachskamm, C., Holsboer, F., and Reul, J. M. (1996) Activation of serotonergic and noradrenergic neurotransmission in the rat hippocampus after peripheral administration of bacterial endotoxin: involvement of the cyclo-oxygenase pathway Neuroscience 72, 989-997
193. Dunn, A. J. (1988) Systemic interleukin-1 administration stimulates hypothalamic norepinephrine metabolism parallelling the increased plasma corticosterone Life Sci. 43, 429-435
194. Kabiersch, A., del Rey, A., Honegger, C. G., and Besedovsky, H. O. (1988) Interleukin-1 induces changes in norepinephrine metabolism in the rat brain Brain, Behav., Immun. 2, 267-274
195. Mohankumar, P. S., Thyagarajan, S., and Quadri, S. K. (1993) Interleukin-1 beta increases 5-hydroxyindoleacetic acid release in the hypothalamus in vivo Brain Res. Bull. 31, 745-748 (Pubitemid 23137797)
196. Dunn, A. J. and Welch, J. (1991) Stress- and endotoxin-induced increases in brain tryptophan and serotonin metabolism depend on sympathetic nervous system activity J. Neurochem. 57, 1615-1622 (Pubitemid 21922797)
197. Maes, M., Verkerk, R., Vandoolaeghe, E., Van Hunsel, F., Neels, H., Wauters, A., Demedts, P., and Scharpe, S. (1997) Serotonin-immune interactions in major depression: lower serum tryptophan as a marker of an immune-inflammatory response Eur. Arch. Psychiatry Clin. Neurosci. 247, 154-161 (Pubitemid 27257585)
198. Zhang, J., Terreni, L., De Simoni, M. G., and Dunn, A. J. (2001) Peripheral interleukin-6 administration increases extracellular concentrations of serotonin and the evoked release of serotonin in the rat striatum Neurochem. Int. 38, 303-308 (Pubitemid 32012990)
199. Masson, J. and Hamon, M. (2009) Monaomine Transporters: Focus on the Regulation of Serotonin Transpoter by Cytokines Encycl. Neurosci. 921-929
200. Mossner, R., Heils, A., Stober, G., Okladnova, O., Daniel, S., and Lesch, K. P. (1998) Enhancement of serotonin transporter function by tumor necrosis factor alpha but not by interleukin-6 Neurochem. Int. 33, 251-254 (Pubitemid 28418296)
201. Ramamoorthy, S., Ramamoorthy, J. D., Prasad, P., Bhat, G. K., Mahesh, V. B., Leibach, F. H., and Ganapathy, V. (1995) Regulation of the human serotonin transporter by interleukin-1β Biochem. Biophys. Res. Commun. 216, 560-567
202. Morikawa, O., Sakai, N., Obara, H., and Saito, N. (1998) Effects of interferon-alpha, interferon-gamma and cAMP on the transcriptional regulation of the serotonin transporter Eur. J. Pharmacol. 349, 317-324 (Pubitemid 28277103)
203. Mössner, R., Daniel, S., Schmitt, A., Albert, D., and Lesch, K. P. (2001) Modulation of serotonin transporter function by interleukin-4 Life Sci. 68, 873-880 (Pubitemid 32168063)
204. Su, S., Zhao, J., Bremner, J. D., Miller, A. H., Tang, W., Bouzyk, M., Snieder, H., Novik, O., Afzal, N., Goldberg, J., and Vaccarino, V. (2009) Serotonin transporter gene, depressive symptoms, and interleukin-6 Circ Cardiovasc Genet 2, 614-620
205. Vogelzangs, N., Duivis, H. E., Beekman, A. T., Kluft, C., Neuteboom, J., Hoogendijk, W., Smit, J. H., de Jonge, P., and Penninx, B. W. (2012) Association of depressive disorders, depression characteristics and antidepressant medication with inflammation Transl Psychiatry 2, e79
206. Dowlati, Y., Herrmann, N., Swardfager, W., Liu, H., Sham, L., Reim, E. K., and Lanctot, K. L. (2010) A meta-analysis of cytokines in major depression Biol. Psychiatry 67, 446-457
207. Howren, M. B., Lamkin, D. M., and Suls, J. (2009) Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis Psychosom. Med. 71, 171-186
208. Prasad, H. C., Zhu, C. B., McCauley, J. L., Samuvel, D. J., Ramamoorthy, S., Shelton, R. C., Hewlett, W. A., Sutcliffe, J. S., and Blakely, R. D. (2005) Human serotonin transporter variants display altered sensitivity to protein kinase G and p38 mitogen-activated protein kinase Proc. Natl. Acad. Sci. U.S.A. 102, 11545-11550 (Pubitemid 41153856)
209. Steiner, J. A., Carneiro, A. M., and Blakely, R. D. (2008) Going with the flow: trafficking-dependent and -independent regulation of serotonin transport Traffic 9, 1393-1402
210. Zhu, C. B., Carneiro, A. M., Dostmann, W. R., Hewlett, W. A., and Blakely, R. D. (2005) p38 MAPK activation elevates serotonin transport activity via a trafficking-independent, protein phosphatase 2A-dependent process J. Biol. Chem. 280, 15649-15658 (Pubitemid 40616683)
211. Qian, Y., Galli, A., Ramamoorthy, S., Risso, S., DeFelice, L. J., and Blakely, R. D. (1997) Protein kinase C activation regulates human serotonin transporters in HEK-293 cells via altered cell surface expression J. Neurosci. 17, 45-47
212. Ramamoorthy, S. and Blakely, R. D. (1998) 5HT-modulates protein kinase C-dependent phosphorylation and trafficking of human serotonin transporter. Presented at the Society for Neuroscience Conference, Los Angeles, CA, 1998.
213. Ramamoorthy, S., Melikian, H. E., Qian, Y., and Blakely, R. D. (1998) Biosynthesis, N-glycosylation, and surface trafficking of biogenic amine transporter proteins Methods Enzymol. 296, 347-370 (Pubitemid 28455032)
214. Zhu, C. B., Hewlett, W. A., Feoktistov, I., Biaggioni, I., and Blakely, R. D. (2004) Adenosine Receptor, Protein kinase G, and p38 mitogen-activated protein kinase-dependent up-regulation of serotonin transporters involves both transporter trafficking and activation Mol. Pharmacol. 65, 1462-1474 (Pubitemid 38668304)
215. Zhu, C. B., Hewlett, W. A., Francis, S. H., Corbin, J. D., and Blakely, R. D. (2004) Stimulation of serotonin transport by the cyclic GMP phosphodiesterase inhibitor sildenafil Eur. J. Pharmacol. 504, 1-6 (Pubitemid 39410716)
216. Ramamoorthy, S., Giovanetti, E., Qian, Y., and Blakely, R. D. (1998) Phosphorylation and regulation of antidepressant-sensitive serotonin transporters J. Biol. Chem. 273, 2458-2466 (Pubitemid 28069306)
217. Ansah, T. A. R., S., Montanez, S., Daws, L. C., and Blakely, R. D. (2003) Calcium-dependent inhibition of synaptosomal serotonin transport by the alpha2-adrenergic receptor agonist UK14304 J. Pharmacol. Exp. Ther. 305, 956-965
218. Daws, L. C., Gould, G. G., Teicher, S. D., Gerhardt, G. A., and Frazer, A. (2000) 5-HT(1B) receptor-mediated regulation of serotonin clearance in rat hippocampus in vivo J. Neurochem. 75, 2113-2122
219. Ramamoorthy, S., Samuvel, D. J., Buck, E. R., Rudnick, G., and Jayanthi, L. D. (2007) Phosphorylation of threonine residue 276 is required for acute regulation of serotonin transporter by cyclic GMP J. Biol. Chem. 282, 11639-11647 (Pubitemid 47100698)
220. Wong, A., Zhang, Y. W., Jeschke, G. R., Turk, B. E., and Rudnick, G. (2012) Cyclic-GMP-dependent stimulation of serotonin transport does not involve direct transporter phosphorylation by cGMP-dependent protein kinase J. Biol. Chem. 287, 36051-36058
221. Chang, J. C., Tomlinson, I. D., Warnement, M. R., Ustione, A., Carneiro, A. M., Piston, D. W., Blakely, R. D., and Rosenthal, S. J. (2012) Single molecule analysis of serotonin transporter regulation using antagonist- conjugated quantum dots reveals restricted, p38 MAPK-dependent mobilization underlying uptake activation J. Neurosci. 32, 8919-8929
222. Zhu, C. B., Blakely, R. D., and Hewlett, W. A. (2006) The Proinflammatory Cytokines Interleukin-1beta and Tumor Necrosis Factor-Alpha Activate Serotonin Transporters Neuropsychopharmacology 31, 2121-2131 (Pubitemid 44413189)
223. Eisenberger, N. I., Berkman, E. T., Inagaki, T. K., Rameson, L. T., Mashal, N. M., and Irwin, M. R. (2010) Inflammation-induced anhedonia: endotoxin reduces ventral striatum responses to reward Biol. Psychiatry 68, 748-754
224. Eisenberger, N. I., Inagaki, T. K., Mashal, N. M., and Irwin, M. R. (2010) Inflammation and social experience: an inflammatory challenge induces feelings of social disconnection in addition to depressed mood Brain, Behav., Immun. 24, 558-563
225. Svenningsson, P., Chergui, K., Rachleff, I., Flajolet, M., Zhang, X., El Yacoubi, M., Vaugeois, J. M., Nomikos, G. G., and Greengard, P. (2006) Alterations in 5-HT1B receptor function by p11 in depression-like states Science 311, 77-80 (Pubitemid 43063061)
226. Warner-Schmidt, J. L., Flajolet, M., Maller, A., Chen, E. Y., Qi, H., Svenningsson, P., and Greengard, P. (2009) Role of p11 in cellular and behavioral effects of 5-HT4 receptor stimulation J. Neurosci. 29, 1937-1946
227. Warner-Schmidt, J. L., Chen, E. Y., Zhang, X., Marshall, J. J., Morozov, A., Svenningsson, P., and Greengard, P. (2010) A role for p11 in the antidepressant action of brain-derived neurotrophic factor Biol. Psychiatry 68, 528-535
228. Dantzer, R. (2001) Cytokine-induced sickness behavior: mechanisms and implications Ann. N.Y. Acad. Sci. 933, 222-234 (Pubitemid 32386037)
229. Kent, S., Bluthe, R. M., Kelley, K. W., and Dantzer, R. (1992) Sickness behavior as a new target for drug development Trends Pharmacol. Sci. 13, 24-28
230. Yirmiya, R., Pollak, Y., Morag, M., Reichenberg, A., Barak, O., Avitsur, R., Shavit, Y., Ovadia, H., Weidenfeld, J., Morag, A., Newman, M. E., and Pollmacher, T. (2000) Illness, cytokines, and depression Ann. N.Y. Acad. Sci. 917, 478-487
231. Lindler, K. M., Baganz, N. L., Zhu, C. B., Deneris, E., Hewlett, W. A., and Blakely, R. D. (2012) Conditional Elimination of p38 MAPK and IL-1 Receptors in Raphe Serotonergic Neurons: Impact on Inflammatory Cytokine Regulation of the Serotonin Transporter and Cytokine-Modulated Behavior. In Society for Neuroscience, New Orleans, LA.
232. Baganz, N. L., Harbom, L. J., Lindler, K. M., Zhu, C. B., and Blakely, R. D. (2012) The role of inflammatory cytokine-linked pathways in anxiety and depressive behavior following maternal separation. In Society for Neuroscience, New Orleans, LA.
233. Bruchas, M. R., Schindler, A. G., Shankar, H., Messinger, D. I., Miyatake, M., Land, B. B., Lemos, J. C., Hagan, C. E., Neumaier, J. F., Quintana, A., Palmiter, R. D., and Chavkin, C. (2011) Selective p38alpha MAPK deletion in serotonergic neurons produces stress resilience in models of depression and addiction Neuron 71, 498-511
234. Patterson, P. H. (2011) Maternal infection and immune involvement in autism Trends Mol. Med. 17, 389-394
235. Ansorge, M. S., Zhou, M., Lira, A., Hen, R., and Gingrich, J. A. (2004) Early-life blockade of the 5-HT transporter alters emotional behavior in adult mice Science 306, 879-881 (Pubitemid 39446998)
236. Gaspar, P., Cases, O., and Maroteaux, L. (2003) The developmental role of serotonin: news from mouse molecular genetics Nat. Rev. Neurosci. 4, 1002-1012 (Pubitemid 37486676)
237. Bonnin, A. and Levitt, P. (2011) Fetal, maternal, and placental sources of serotonin and new implications for developmental programming of the brain Neuroscience 197, 1-7