Chronic toxoplasma gondii in nurr1-null heterozygous mice exacerbates elevated open field activity

PLoS ONE

Volumn 10, Issue 4, 2015, Pages

  Eells, Jeffrey B ^a   Varela Stokes, Andrea ^a   Guo Ross, Shirley X ^a   Kummari, Evangel ^a   Smith, Holly M ^a   Cox, Erin ^a   Lindsay, David S ^b  

^a MISSISSIPPI STATE UNIVERSITY   (United States)

^b VIRGINIA MARYLAND REGIONAL COLLEGE OF VETERINARY MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

NUCLEAR RECEPTOR RELATED FACTOR 1; NR4A2 PROTEIN, MOUSE; PARASITE ANTIGEN;

ANIMAL BEHAVIOR; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIBODY TITER; ARTICLE; AVERSIVE BEHAVIOR; CONTROLLED STUDY; DISEASE PREDISPOSITION; FEMALE; GENE; GENOTYPE; GENOTYPE ENVIRONMENT INTERACTION; IMMUNE RESPONSE; LYNX RUFUS; MALE; MOUSE; NEUROTRANSMISSION; NONHUMAN; NOVEL OBJECT RECOGNITION TEST; NURR1 GENE; OPEN FIELD BEHAVIOR; SENSORY GATING; STARTLE REFLEX; TASK PERFORMANCE; TOXOPLASMA GONDII; TOXOPLASMOSIS; URINE; ANIMAL; ANXIETY; AVOIDANCE BEHAVIOR; BODY WEIGHT; CHRONIC DISEASE; DEFICIENCY; GENE DELETION; GENETICS; HETEROZYGOTE; IMMUNOLOGY; PARASITOLOGY; PATHOPHYSIOLOGY; PHYSIOLOGY; PSYCHOLOGY; SCHIZOPHRENIA; SEROCONVERSION; TOXOPLASMA;

ANIMALIA; LYNX RUFUS; MURINAE; MUS; TOXOPLASMA GONDII;

ANIMALS; ANTIGENS, PROTOZOAN; ANXIETY; AVOIDANCE LEARNING; BEHAVIOR, ANIMAL; BODY WEIGHT; CHRONIC DISEASE; FEMALE; GENE DELETION; GENOTYPE; HETEROZYGOTE; MALE; MICE; NUCLEAR RECEPTOR SUBFAMILY 4, GROUP A, MEMBER 2; REFLEX, STARTLE; SCHIZOPHRENIA; SENSORY GATING; SEROCONVERSION; TOXOPLASMA; TOXOPLASMOSIS;

EID: 84929486150     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0119280     Document Type: Article

References (114)

1. Need AC, McEvoy JP, Gennarelli M, Heinzen EL, Ge D, Maia JM, et al. Exome sequencing followed by large-scale genotyping suggests a limited role for moderately rare risk factors of strong effect in schizophrenia. Am J Hum Genet. 2012; 91: 303-312. doi:10.1016/j.ajhg.2012.06.018 PMID: 22863191.
2. Stefansson H, Ophoff RA, Steinberg S, Andreassen OA, Cichon S, Rujescu D, et al. Common variants conferring risk of schizophrenia. Nature. 2009; 460: 744-747. doi:10.1038/nature08186 PMID: 19571808.
3. Brown AS (2011) The environment and susceptibility to schizophrenia. Prog Neurobiol 93: 23-58. doi:10.1016/j.pneurobio.2010.09.003 PMID: 20955757.
4. Torrey EF, Bartko JJ, Yolken RH. Toxoplasma gondii and other risk factors for schizophrenia: An update. Schizophr Bull. 2012; 38: 642-647. doi:10.1093/schbul/sbs043 PMID: 22446566.
5. Tenter AM, Heckeroth AR, Weiss LM. Toxoplasma gondii: from animals to humans. Int J Parasitol. 2000; 30: 1217-1258. PMID: 11113252.
6. Flegr J. Effects of toxoplasma on human behavior. Schizophr Bull. 2007; 33: 757-760. PMID: 17218612.
7. Flegr J. How and why Toxoplasma makes us crazy. Trends Parasitol. 2013; 29: 156-163. doi:10.1016/j.pt.2013.01.007 PMID: 23433494.
8. Flegr J. Influence of latent Toxoplasma infection on human personality, physiology and morphology: pros and cons of the Toxoplasma-human model in studying the manipulation hypothesis. J Exp Biol. 2013; 216: 127-133. doi: 10.1242/jeb.073635 PMID: 23225875.
9. Holub D, Flegr J, Dragomirecka E, Rodriguez M, Preiss M, Novak T, et al. Differences in onset of disease and severity of psychopathology between toxoplasmosis-related and toxoplasmosis-unrelated schizophrenia. Acta Psychiatr Scand. 2013; 127: 227-238. doi:10.1111/acps.12031 PMID: 23126494.
10. McConkey GA, Martin HL, Bristow GC, Webster JP. Toxoplasma gondii infection and behaviour-location, location, location? J Exp Biol. 2013; 216: 113-119. doi:10.1242/jeb.074153 PMID: 23225873.
11. Torrey EF, Yolken RH. Toxoplasma gondii and schizophrenia. Emerg Infect Dis. 2003; 9: 1375-1380. PMID: 14725265.
12. Torrey EF, Yolken RH. Schizophrenia and toxoplasmosis. Schizophr Bull. 2007; 33: 727-728. PMID: 17426051.
13. Yolken RH, Dickerson FB, Fuller Torrey E. Toxoplasma and schizophrenia. Parasite Immunol. 2009; 31: 706-715. doi:10.1111/j.1365-3024.2009.01131.x PMID: 19825110.
14. Horacek J, Flegr J, Tintera J, Verebova K, Spaniel F, Novak T, et al. Latent toxoplasmosis reduces gray matter density in schizophrenia but not in controls: voxel-based-morphometry (VBM) study. World J Biol Psychiatry. 2012; 13: 501-509. doi:10.3109/15622975.2011.573809 PMID: 21599563.
15. Blomström A, Karlsson H, Wicks S, Yang S, Yolken RH, Dalman C. Maternal antibodies to infectious agents and risk for non-affective psychoses in the offspring-a matched case-control study. Schizophr Res. 2012; 140: 25-30. doi:10.1016/j.schres.2012.06.035 PMID: 22819777.
16. Brown AS, Schaefer CA, Quesenberry CP Jr., Liu L, Babulas VP, Susser ES. Maternal exposure to toxoplasmosis and risk of schizophrenia in adult offspring. Am J Psychiatry. 2005; 162: 767-773. PMID: 15800151.
17. Mortensen PB, Norgaard-Pedersen B, Waltoft BL, Sorensen TL, Hougaard D, Yolken RH. Early infections of Toxoplasma gondii and the later development of schizophrenia. Schizophr Bull. 2007; 33: 741-744. PMID: 17329231.
18. Brown AS, Derkits EJ. Prenatal infection and schizophrenia: A review of epidemiologic and translational studies. Am J Psychiatry. 2010; 167: 261-280. doi:10.1176/appi.ajp.2009.09030361 PMID: 20123911.
19. Jones JL, Kruszon-Moran D, Sanders-Lewis K, Wilson M. Toxoplasma gondii infection in the United States, 1999 2004, decline from the prior decade. Am J Trop Med Hyg. 2007; 77: 405-410. PMID: 17827351.
20. Stibbs HH. Changes in brain concentrations of catecholamines and indoleamines in Toxoplasma gondii infected mice. Ann Trop Med Parasitol. 1985; 79: 153-157. PMID: 2420295.
21. Gaskell EA, Smith JE, Pinney JW, Westhead DR, McConkey GA. A unique dual activity amino acid hydroxylase in Toxoplasma gondii. PLoS One. 2009; 4: e4801. doi:10.1371/journal.pone.0004801 PMID: 19277211.
22. Prandovszky E, Gaskell E, Martin H, Dubey JP, Webster JP, McConkey GA. The neurotropic parasite Toxoplasma gondii increases dopamine metabolism. PLoS One. 2011; 6: e23866. doi:10.1371/journal.pone.0023866 PMID: 21957440.
23. Hay J, Aitken PP, Graham DI. Toxoplasma infection and response to novelty in mice. Z Parasitenkd 1984; 70: 575-588. PMID: 6506841.
24. Hay J, Hutchison WM, Aitken PP, Graham DI. The effect of congenital and adult-acquired Toxoplasma infections on activity and responsiveness to novel stimulation in mice. Ann Trop Med Parasitol 1983; 77: 483-495. PMID: 6660954.
25. Webster JP. The effect of Toxoplasma gondii on animal behavior: playing cat and mouse. Schizophr Bull. 2007; 33: 752-756. PMID: 17218613.
26. Xiao J, Kannan G, Jones-Brando L, Brannock C, Krasnova IN, Cadet JL, et al. Sex-specific changes in gene expression and behavior induced by chronic Toxoplasma infection in mice. Neuroscience 2012; 206: 39-48. doi:10.1016/j.neuroscience.2011.12.051 PMID: 22240252.
27. Lau CI, Wang HC, Hsu JL, Liu ME. Does the dopamine hypothesis explain schizophrenia? Rev Neurosci 2013; 24: 389-400. doi:10.1515/revneuro-2013-0011 PMID: 23843581.
28. Miyake N, Thompson J, Skinbjerg M, Abi-Dargham A. Presynaptic dopamine in schizophrenia. CNS Neurosci Ther. 2011; 17: 104-109. doi:10.1111/j.1755-5949.2010.00230.x PMID: 21199451.
29. Seeman P. Schizophrenia and dopamine receptors. Eur Neuropsychopharmacol. 2013; 23: 999- 1009. doi:10.1016/j.euroneuro.2013.06.005 PMID: 23860356.
30. Castillo SO, Baffi JS, Palkovits M, Goldstein DS, Kopin IJ, Witta J, et al. Dopamine biosynthesis is selectively abolished in substantia nigra/ventral tegmental area but not in hypothalamic neurons in mice with targeted disruption of the Nurr1 gene. Mol Cell Neurosci. 1998; 11: 36-46. PMID: 9608532.
31. Kadkhodaei B, Ito T, Joodmardi E, Mattsson B, Rouillard C, Carta M, et al. Nurr1 is required for maintenance of maturing and adult midbrain dopamine neurons. J Neurosci. 2009; 29: 15923-15932. doi:10.1523/JNEUROSCI.3910-09.2009 PMID: 20016108.
32. Saucedo-Cardenas O, Quintana-Hau JD, Le WD, Smidt MP, Cox JJ, De Mayo F, et al. Nurr1 is essential for the induction of the dopaminergic phenotype and the survival of ventral mesencephalic late dopaminergic precursor neurons. Proc Natl Acad Sci U S A. 1998; 95: 4013-4018. PMID: 9520484.
33. Zetterström RH, Solomin L, Jansson L, Hoffer BJ, Olson L, Perlmann T. Dopamine neuron agenesis in Nurr1-deficient mice. Science. 1997; 276: 248-250. PMID: 9092472.
34. Buervenich S, Carmine A, Arvidsson M, Xiang F, Zhang Z, Sydow O, et al. NURR1 mutations in cases of schizophrenia and manic-depressive disorder. Am J Med Genet. 2000; 96: 808-813. PMID: 11121187.
35. Chen YH, Tsai MT, Shaw CK, Chen CH. Mutation analysis of the human NR4A2 gene, an essential gene for midbrain dopaminergic neurogenesis, in schizophrenic patients. Am J Med Genet. 2001; 105: 753-757. PMID: 11803525.
36. Ancin I, Cabranes JA, Vazquez-Alvarez B, Santos JL, Sanchez-Morla E, et al. NR4A2: effects of an "orphan" receptor on sustained attention in a schizophrenic population. Schizophr Bull. 2013; 39: 555-563. doi:10.1093/schbul/sbr176PMID: 22294735.
37. Eells JB, Yeung SK, Nikodem VM. Dopamine neurons heterozygous for the Nurr1-Null allele have reduced survival in vitro. Neurosci Res Comm. 2002; 30: 173-183.
38. Eells JB, Misler JA, Nikodem VM. Early postnatal isolation reduces dopamine levels, elevates dopamine turnover and specifically disrupts prepulse inhibition in Nurr1-null heterozygous mice. Neuroscience. 2006; 140: 1117-1126. PMID: 16690213.
39. Rojas P, Joodmardi E, Hong Y, Perlmann T, Ogren SO. Adult mice with reduced Nurr1 expression: An animal model for schizophrenia. Mol Psychiatry. 2007; 12: 756-766. PMID: 17457314.
40. Vuillermot S, Joodmardi E, Perlmann T, Ogren SO, Feldon J, Meyer U. Schizophrenia-relevant behaviors in a genetic mouse model of constitutive Nurr1 deficiency. Genes Brain Behav. 2011; 10: 589-603. doi:10.1111/j.1601-183X.2011.00698.x PMID: 21545404.
41. Braff DL, Swerdlow NR, Geyer MA. Gating and habituation deficits in the schizophrenia disorders. Clin Neurosci. 1995; 3: 131-139. PMID: 7583619.
42. Braff DL, Swerdlow NR, Geyer MA. Symptom correlates of prepulse inhibition deficits in male schizophrenic patients. Am J Psychiatry. 1999; 156: 596-602. PMID: 10200740.
43. Duncan EJ, Szilagyi S, Efferen TR, Schwartz MP, Parwani A, Chakravorty S, et al. Effect of treatment status on prepulse inhibition of acoustic startle in schizophrenia. Psychopharmacology (Berl). 2003; 167: 63-71. PMID: 12632245.
44. Light GA, Braff DL. Human and animal studies of schizophrenia-related gating deficits. Curr Psychiatry Rep. 1999; 1: 31-40. PMID: 11122903.
45. Ludewig K, Geyer MA, Etzensberger M, Vollenweider FX. Stability of the acoustic startle reflex, prepulse inhibition, and habituation in schizophrenia. Schizophr Res. 2002; 55: 129-137. PMID: 11955972.
46. Ludewig K, Geyer MA, Vollenweider FX. Deficits in prepulse inhibition and habituation in never-medicated, first-episode schizophrenia. Biol Psychiatry. 2003; 54: 121-128. PMID: 12873801.
47. Mackeprang T, Kristiansen KT, Glenthoj BY. Effects of antipsychotics on prepulse inhibition of the startle response in drug-naive schizophrenic patients. Biol Psychiatry. 2002; 52: 863-873. PMID: 12399139.
48. Moore TM, Brown T, Cade M, Eells JB. Alterations in amphetamine-stimulated dopamine overflow due to the Nurr1-null heterozygous genotype and postweaning isolation. Synapse. 2008; 62: 764- 774. doi:10.1002/syn.20550 PMID: 18655117.
49. Dulawa SC, Grandy DK, Low MJ, Paulus MP, Geyer MA. Dopamine D4 receptor-knock-out mice exhibit reduced exploration of novel stimuli. J Neurosci. 1999; 19: 9550-9556. PMID: 10531457.
50. Eells JB, Lipska BK, Yeung SK, Misler JA, Nikodem VM. Nurr1-null heterozygous mice have reduced mesolimbic and mesocortical dopamine levels and increased stress-induced locomotor activity. Behav Brain Res. 2002; 136: 267-275. PMID: 12385813.
51. Vuillermot S, Feldon J, Meyer U. Nurr1 is not essential for the development of prepulse inhibition deficits induced by prenatal immune activation. Brain Behav Immun. 2011; 25: 1316-1321. doi:10.1016/j.bbi.2011.06.012 PMID: 21723940.
52. Giros B, Jaber M, Jones SR, Wightman RM, Caron MG. Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter. Nature. 1996; 379: 606-612. PMID: 8628395.
53. Lacroix L, Broersen LM, Feldon J, Weiner I. Effects of local infusions of dopaminergic drugs into the medial prefrontal cortex of rats on latent inhibition, prepulse inhibition and amphetamine induced activity. Behav Brain Res. 2000; 107: 111-121. PMID: 10628735.
54. Ralph RJ, Paulus MP, Geyer MA. Strain-specific effects of amphetamine on prepulse inhibition and patterns of locomotor behavior in mice. J Pharmacol Exp Ther. 2001; 298: 148-155. PMID: 11408536.
55. Fernagut PO, Diguet E, Jaber M, Bioulac B, Tison F. Dopamine transporter knock-out mice are hypersensitive to 3-nitropropionic acid-induced striatal damage. Eur J Neurosci. 2002; 15: 2053-2056. PMID: 12099912.
56. Spielewoy C, Roubert C, Hamon M, Nosten-Bertrand M, Betancur C, Giros B. Behavioural disturbances associated with hyperdopaminergia in dopamine-transporter knockout mice. Behav Pharmacol. 2000; 11: 279-290. PMID: 11103882.
57. Takahashi N, Miner LL, Sora I, Ujike H, Revay RS, Kostic V, et al. VMAT2 knockout mice: Heterozygotes display reduced amphetamine-conditioned reward, enhanced amphetamine locomotion, and enhanced MPTP toxicity. Proc Natl Acad Sci U S A. 1997; 94: 9938-9943. PMID: 9275230.
58. Zhuang X, Oosting RS, Jones SR, Gainetdinov RR, Miller GW, Caron MG, et al. Hyperactivity and impaired response habituation in hyperdopaminergic mice. Proc Natl Acad Sci U S A. 2001; 98: 1982- 1987. PMID: 11172062.
59. Kadkhodaei B, Alvarsson A, Schintu N, Ramskold D, Volakakis N, Joodmardi E, et al. Transcription factor Nurr1 maintains fiber integrity and nuclear-encoded mitochondrial gene expression in dopamine neurons. Proc Natl Acad Sci U S A. 2013; 110: 2360-2365. doi:10.1073/pnas.1221077110 PMID: 23341612.
60. Eells JB, Misler JA, Nikodem VM. Reduced tyrosine hydroxylase and GTP cyclohydrolase mRNA expression, tyrosine hydroxylase activity, and associated neurochemical alterations in Nurr1-null heterozygous mice. Brain Res Bull. 2006; 70: 186-195. PMID: 16782508.
61. Hay J, Aitken PP, Arnott MA. The influence of congenital Toxoplasma infection on the spontaneous running activity of mice. Z Parasitenkd. 1985; 71: 459-462. PMID: 4040684.
62. Hutchinson WM, Bradley M, Cheyne WM, Wells BW, Hay J. Behavioural abnormalities in Toxoplasma- infected mice. Ann Trop Med Parasitol. 1980; 74: 337-345. PMID: 7396566.
63. Gulinello M, Acquarone M, Kim JH, Spray DC, Barbosa HS, Sellers R, et al. Acquired infection with Toxoplasma gondii in adult mice results in sensorimotor deficits but normal cognitive behavior despite widespread brain pathology. Microbes Infect. 2010; 12: 528-537. doi:10.1016/j.micinf.2010.03.009 PMID: 20348009.
64. Skallova A, Kodym P, Frynta D, Flegr J. The role of dopamine in Toxoplasma-induced behavioural alterations in mice: An ethological and ethopharmacological study. Parasitology. 2006; 133: 525-535. PMID: 16882355.
65. Vyas A, Kim SK, Giacomini N, Boothroyd JC, Sapolsky RM. Behavioral changes induced by Toxoplasma infection of rodents are highly specific to aversion of cat odors. Proc Natl Acad Sci U S A. 2007; 104: 6442-6447. PMID: 17404235.
66. Vyas A, Kim SK, Sapolsky RM. The effects of toxoplasma infection on rodent behavior are dependent on dose of the stimulus. Neuroscience. 2007; 148: 342-348. PMID: 17683872.
67. Braff DL, Geyer MA, Swerdlow NR. Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies. Psychopharmacology (Berl). 2001; 156: 234-258. PMID: 11549226.
68. Geyer MA, Krebs-Thomson K, Braff DL, Swerdlow NR. Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: A decade in review. Psychopharmacology (Berl). 2001; 156: 117-154. PMID: 11549216.
69. Ralph RJ, Paulus MP, Fumagalli F, Caron MG, Geyer MA. Prepulse inhibition deficits and perseverative motor patterns in dopamine transporter knock-out mice: Differential effects of D1 and D2 receptor antagonists. J Neurosci. 2001; 21: 305-313. PMID: 11150348.
70. Swerdlow NR, Braff DL, Masten VL, Geyer MA. Schizophrenic-like sensorimotor gating abnormalities in rats following dopamine infusion into the nucleus accumbens. Psychopharmacology (Berl). 1990; 101: 414-420. PMID: 2114026.
71. Arias I, Sorlozano A, Villegas E, de Dios Luna J, McKenney K, Cervilla J, et al. Infectious agents associated with schizophrenia: A meta-analysis. Schizophr Res. 2012; 136: 128-136. doi:10.1016/j.schres.2011.10.026 PMID: 22104141.
72. Kuepper R, Skinbjerg M, Abi-Dargham A. The dopamine dysfunction in schizophrenia revisited: new insights into topography and course. Handb Exp Pharmacol. 2012:1-26.
73. Lieberman JA, Koreen AR. Neurochemistry and neuroendocrinology of schizophrenia: A selective review. Schizophr Bull. 1993; 19: 371-429. PMID: 8100644.
74. Lodge DJ, Grace AA. Hippocampal dysregulation of dopamine system function and the pathophysiology of schizophrenia. Trends Pharmacol Sci. 2011; 32: 507-513. doi:10.1016/j.tips.2011.05.001 PMID: 21700346.
75. Seeman P. All roads to schizophrenia lead to dopamine supersensitivity and elevated dopamine D2 (high) receptors. CNS Neurosci Ther. 2011; 17: 118-132. doi:10.1111/j.1755-5949.2010.00162.x PMID: 20560996.
76. Torrey EF, Bartko JJ, Lun ZR, Yolken RH. Antibodies to Toxoplasma gondii in patients with schizophrenia: A meta-analysis. Schizophr Bull. 2007; 33: 729-736. PMID: 17085743.
77. Abi-Dargham A. Do we still believe in the dopamine hypothesis? New data bring new evidence. Int J Neuropsychopharmacol. 2004; 7 Suppl 1: S1-S5. PMID: 14972078.
78. Howes OD, Kambeitz J, Kim E, Stahl D, Slifstein M, Abi-Dargham A, et al. The nature of dopamine dysfunction in schizophrenia and what this means for treatment. Arch Gen Psychiatry. 2012; 69: 776- 786. PMID: 22474070.
79. Carruthers VB, Suzuki Y. Effects of Toxoplasma gondii infection on the brain. Schizophr Bull. 2007; 33: 745-751. PMID: 17322557.
80. Sims TA, Hay J, Talbot IC. Ultrastructural immunocytochemistry of the intact tissue cyst of Toxoplasma in the brains of mice with congenital toxoplasmosis. Ann Trop Med Parasitol. 1990; 84: 141-147. PMID: 2383094.
81. Schwarcz R, Bruno JP, Muchowski PJ, Wu HQ. Kynurenines in the mammalian brain: when physiology meets pathology. Nat Rev Neurosci. 2012; 13: 465-477. doi:10.1038/nrn3257 PMID: 22678511.
82. Hilmas C, Pereira EF, Alkondon M, Rassoulpour A, Schwarcz R, Albuquerque EX. The brain metabolite kynurenic acid inhibits alpha7 nicotinic receptor activity and increases non-alpha7 nicotinic receptor expression: physiopathological implications. J Neurosci. 2001; 21: 7463-7473. PMID: 11567036.
83. Parsons CG, Danysz W, Quack G, Hartmann S, Lorenz B, Wollenburg C, et al. Novel systemically active antagonists of the glycine site of the N-methyl-D-aspartate receptor: electrophysiological, biochemical and behavioral characterization. J Pharmacol Exp Ther. 1997; 283: 1264-1275. PMID: 9400002.
84. Perkins MN, Stone TW. An iontophoretic investigation of the actions of convulsant kynurenines and their interaction with the endogenous excitant quinolinic acid. Brain Res. 1982; 247: 184-187. PMID: 6215086.
85. Stone TW, Stoy N, Darlington LG. An expanding range of targets for kynurenine metabolites of tryptophan. Trends Pharmacol Sci. 2013; 34: 136-143. doi:10.1016/j.tips.2012.09.006 PMID: 23123095.
86. Eastwood SL, Heffernan J, Harrison PJ. Chronic haloperidol treatment differentially affects the expression of synaptic and neuronal plasticity-associated genes. Mol Psychiatry. 1997; 2: 322-329. PMID: 9246673.
87. Erhardt S, Schwieler L, Emanuelsson C, Geyer M. Endogenous kynurenic acid disrupts prepulse inhibition. Biol Psychiatry. 2004; 56: 255-260. PMID: 15312813.
88. Olsson SK, Andersson AS, Linderholm KR, Holtze M, Nilsson-Todd LK, Schwieler L, et al. Elevated levels of kynurenic acid change the dopaminergic response to amphetamine: implications for schizophrenia. Int J Neuropsychopharmacol. 2009; 12: 501-512. doi:10.1017/S1461145708009383 PMID: 18796185.
89. Linderholm KR, Andersson A, Olsson S, Olsson E, Snodgrass R, Engberg G, et al. Activation of rat ventral tegmental area dopamine neurons by endogenous kynurenic acid: A pharmacological analysis. Neuropharmacology. 2007; 53: 918-924. PMID: 17959203.
90. Notarangelo FM, Wilson EH, Horning KJ, Thomas MA, Harris TH, Fang Q, et al. Evaluation of kynurenine pathway metabolism in Toxoplasma gondii-infected mice: implications for schizophrenia. Schizophr Res. 2014; 152: 261-267. doi:10.1016/j.schres.2013.11.011 PMID: 24345671.
91. Schwarcz R, Hunter CA. Toxoplasma gondii and schizophrenia: linkage through astrocyte-derived kynurenic acid? Schizophr Bull. 2007; 33: 652-653. PMID: 17434932.
92. Erhardt S, Blennow K, Nordin C, Skogh E, Lindstrom LH, Engberg G. Kynurenic acid levels are elevated in the cerebrospinal fluid of patients with schizophrenia. Neurosci Lett 313: 96-98. PMID: 11684348.
93. Linderholm KR, Skogh E, Olsson SK, Dahl ML, Holtze M, Engberg G, et al. Increased levels of kynurenine and kynurenic acid in the CSF of patients with schizophrenia. Schizophr Bull. 2012; 38: 426-432. doi:10.1093/schbul/sbq086 PMID: 20729465.
94. Miller CL, Llenos IC, Dulay JR, Weis S. Upregulation of the initiating step of the kynurenine pathway in postmortem anterior cingulate cortex from individuals with schizophrenia and bipolar disorder. Brain Res. 2006; 1073-1074: 25-37.
95. Muller N, Schwarz M. Schizophrenia as an inflammation-mediated dysbalance of glutamatergic neurotransmission. Neurotox Res. 2006; 10: 131-148. PMID: 17062375.
96. Schwarcz R, Rassoulpour A, Wu HQ, Medoff D, Tamminga CA, Roberts RC. Increased cortical kynurenate content in schizophrenia. Biol Psychiatry. 2001; 50: 521-530. PMID: 11600105.
97. Wonodi I, Stine OC, Sathyasaikumar KV, Roberts RC, Mitchell BD, Hong LE, et al. Downregulated kynurenine 3-monooxygenase gene expression and enzyme activity in schizophrenia and genetic association with schizophrenia endophenotypes. Arch Gen Psychiatry. 2011; 68: 665-674. doi:10.1001/archgenpsychiatry.2011.71 PMID: 21727251.
98. Keller WR, Kum LM, Wehring HJ, Koola MM, Buchanan RW, Kelly DL. A review of anti-inflammatory agents for symptoms of schizophrenia. J Psychopharmacol. 2013; 27: 337-342. doi:10.1177/0269881112467089 PMID: 23151612.
99. Muller N. The role of anti-inflammatory treatment in psychiatric disorders. Psychiatr Danub. 2013; 25: 292-298. PMID: 24048400.
100. Sesack SR, Carr DB. Selective prefrontal cortex inputs to dopamine cells: implications for schizophrenia. Physiol Behav. 2002; 77: 513-517. PMID: 12526992.
101. Felger JC, Miller AH. Cytokine effects on the basal ganglia and dopamine function: The subcortical source of inflammatory malaise. Front Neuroendocrinol. 2012; 33: 315-327. doi:10.1016/j.yfrne.2012.09.003 PMID: 23000204.
102. Seeman MV, Seeman P. Is schizophrenia a dopamine supersensitivity psychotic reaction? Prog Neuropsychopharmacol Biol Psychiatry. 2014; 48: 155-160. doi:10.1016/j.pnpbp.2013.10.003 PMID: 24128684.
103. Ayhan Y, Sawa A, Ross CA, Pletnikov MV. Animal models of gene-environment interactions in schizophrenia. Behav Brain Res. 2009; 204: 274-281. doi:10.1016/j.bbr.2009.04.010 PMID: 19379776.
104. Mouri A, Nagai T, Ibi D, Yamada K. Animal models of schizophrenia for molecular and pharmacological intervention and potential candidate molecules. Neurobiol Dis. 2013; 53: 61-74. doi:10.1016/j.nbd.2012.10.025PMID: 23142533.
105. Nagai T, Ibi D, Yamada K. Animal model for schizophrenia that reflects gene-environment interactions. Biol Pharm Bull. 2011; 34: 1364-1368. PMID: 21881218.
106. Eells JB, Wilcots J, Sisk S, Guo-Ross SX. NR4A gene expression is dynamically regulated in the ventral tegmental area dopamine neurons and is related to expression of dopamine neurotransmission genes. J Mol Neurosci. 2012; 46: 545-553. doi:10.1007/s12031-011-9642-z PMID: 21932041.
107. Hermanson E, Joseph B, Castro D, Lindqvist E, Aarnisalo P, Wallen A, et al. Nurr1 regulates dopamine synthesis and storage in MN9D dopamine cells. Exp Cell Res. 2003; 288: 324-334. PMID: 12915123.
108. Sacchetti P, Mitchell TR, Granneman JG, Bannon MJ. Nurr1 enhances transcription of the human dopamine transporter gene through a novel mechanism. J Neurochem. 2001; 76: 1565-1572. PMID: 11238740.
109. Xiao J, Li Y, Prandovszky E, Karuppagounder SS, Talbot CC Jr., Dawson VL, et al. MicroRNA-132 dysregulation in Toxoplasma gondii infection has implications for dopamine signaling pathway. Neuroscience. 2014; 268: 128-138. doi:10.1016/j.neuroscience.2014.03.015 PMID: 24657774.
110. Yang D, Li T, Wang Y, Tang Y, Cui H, Tang Y, et al. miR-132 regulates the differentiation of dopamine neurons by directly targeting Nurr1 expression. J Cell Sci. 2012; 125: 1673-1682. doi:10.1242/jcs.086421 PMID: 22328530.
111. Saijo K, Winner B, Carson CT, Collier JG, Boyer L, Rosenfeld MG, et al. A Nurr1/CoREST pathway in microglia and astrocytes protects dopaminergic neurons from inflammation-induced death. Cell. 2009; 137: 47-59. doi:10.1016/j.cell.2009.01.038 PMID: 19345186.
112. Hermes G, Ajioka JW, Kelly KA, Mui E, Roberts F, Kasza K, et al. Neurological and behavioral abnormalities, ventricular dilatation, altered cellular functions, inflammation, and neuronal injury in brains of mice due to common, persistent, parasitic infection. J Neuroinflammation. 2008; 5: 48. doi:10.1186/1742-2094-5-48 PMID: 18947414.
113. Hinze-Selch D, Daubener W, Eggert L, Erdag S, Stoltenberg R, Wilms S. A controlled prospective study of toxoplasma gondii infection in individuals with schizophrenia: Beyond seroprevalence. Schizophr Bull. 2007; 33: 782-788. PMID: 17387159.
114. Ramanathan S, Mohammad SS, Brilot F, Dale RC. Autoimmune encephalitis: Recent updates and emerging challenges. J Clin Neurosci. 2013; 21: 722-730. doi:10.1016/j.jocn.2013.07.017 PMID: 24246947.