Schizophrenia: Do all roads lead to dopamine or is this where they start Evidence from two epidemiologically informed developmental rodent models

Translational Psychiatry

Volumn 2, Issue , 2012, Pages

  Eyles, D ^a,b   Feldon, J ^c   Meyer, U ^c  

^a UNIVERSITY OF QUEENSLAND   (Australia)

^b QUEENSLAND CENTRE FOR MENTAL HEALTH RESEARCH   (Australia)

^c ETH ZURICH   (Switzerland)

Author keywords

Brain development; Dopamine; Maternal immune activation; Ontogeny; Schizophrenia; Vitamin D

Indexed keywords

3,4 DIHYDROXYPHENYLACETIC ACID; AMPHETAMINE; CALCITRIOL; CATECHOL METHYLTRANSFERASE; DOPAMINE; FIBROBLAST GROWTH FACTOR 8; HALOPERIDOL; N METHYL DEXTRO ASPARTIC ACID RECEPTOR BLOCKING AGENT; NORADRENALIN; POLYINOSINIC POLYCYTIDYLIC ACID; SONIC HEDGEHOG PROTEIN; TYROSINE 3 MONOOXYGENASE; VITAMIN D; CYTOKINE; INTERFERON INDUCING AGENT;

BEHAVIOR; BEHAVIOR DISORDER; BRAIN DEVELOPMENT; BRAIN FUNCTION; COGNITION; DOPAMINERGIC SYSTEM; EMBRYO DEVELOPMENT; ENVIRONMENTAL FACTOR; EPIDEMIOLOGICAL DATA; EXPERIMENTAL MODEL; EXPLORATORY BEHAVIOR; HABITUATION; HEREDITY; HIPPOCAMPUS; HUMAN; IMMUNE RESPONSE; INFLAMMATION; LEARNING; LOCOMOTION; LONG TERM POTENTIATION; MEMORY; NONHUMAN; ONTOGENY; PRENATAL EXPOSURE; PROGENY; REVIEW; RISK ASSESSMENT; RISK FACTOR; RODENT; SCHIZOPHRENIA; SELECTIVE ATTENTION; SENSORY DYSFUNCTION; SENSORY GATING; SIGNAL TRANSDUCTION; SOCIAL INTERACTION; VITAMIN D DEFICIENCY; WORKING MEMORY; ANIMAL; ATTENTION; BRAIN; DISEASE MODEL; FEMALE; FETOMATERNAL TRANSFUSION; IMMUNOLOGY; MOTOR ACTIVITY; MOUSE; PATHOPHYSIOLOGY; PHYSIOLOGY; PREGNANCY; RAT;

ANIMALS; ATTENTION; BRAIN; CYTOKINES; DISEASE MODELS, ANIMAL; DOPAMINE; FEMALE; INTERFERON INDUCERS; MATERNAL-FETAL EXCHANGE; MICE; MOTOR ACTIVITY; POLY I-C; PREGNANCY; PRENATAL EXPOSURE DELAYED EFFECTS; RATS; SCHIZOPHRENIA; SENSORY GATING; SIGNAL TRANSDUCTION; VITAMIN D DEFICIENCY;

EID: 84858025838     PISSN: None     EISSN: 21583188     Source Type: Journal    
DOI: 10.1038/tp.2012.6     Document Type: Review

References (132)

1. McGrath JJ, Feron FP, Burne TH, Mackay-Sim A, Eyles DW. The neurodevelopmental hypothesis of schizophrenia: a review of recent developments. Ann Med 2003; 35: 86-93. (Pubitemid 36638211)
2. Weinberger DR. Implications of normal brain development for the pathogenesis of schizophrenia. Arch Gen Psychiatry 1987; 44: 660-669. (Pubitemid 17099795)
3. van Os J, Kenis G, Rutten BP. The environment and schizophrenia. Nature 2010; 468: 203-212.
4. McClellan J, King MC. Genetic heterogeneity in human disease. Cell 2010; 141: 210-217.
5. Need AC, Ge D, Weale ME, Maia J, Feng S, Heinzen EL et al. A genome-wide investigation of SNPs and CNVs in schizophrenia. PLoS Genet 2009; 5: e1000373.
6. Ripke S, Sanders AR, Kendler KS, Levinson DF, Sklar P, Holmans PA et al. Genomewide association study identifies five new schizophrenia loci. Nat Genet 2011; 43: 969-976.
7. Toda M, Abi-Dargham A. Dopamine hypothesis of schizophrenia: making sense of it all. Curr Psychiatry Rep 2007; 9: 329-336. (Pubitemid 47490006)
8. Carlsson A, Lindqvist M. Effect of chlorpromazine or haloperidol on formation of 3 methoxytyramine and normetanephrine in mouse brain. Acta Pharmacol Toxicol (Copenh) 1963; 20: 140-144.
9. Davis KL, Kahn RS, Ko G, Davidson M. Dopamine in schizophrenia: a review and reconceptualization. Am J Psychiatry 1991; 148: 1474-1486.
10. Abi-Dargham A, Mawlawi O, Lombardo I, Gil R, Martinez D, Huang Y et al. Prefrontal dopamine D1 receptors and working memory in schizophrenia. J Neurosci 2002; 22: 3708-3719. (Pubitemid 37465776)
11. Kapur S, Mamo D. Half a century of antipsychotics and still a central role for dopamine D2 receptors. Prog Neuropsychopharmacol Biol Psychiatry 2003; 27: 1081-1090. (Pubitemid 37464954)
12. Breier A, Su TP, Saunders R, Carson RE, Kolachana BS, de Bartolomeis A et al. Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations: evidence from a novel positron emission tomography method. Proc Natl Acad Sci USA 1997; 94: 2569-2574. (Pubitemid 27136916)
13. Abi-Dargham A, Gil R, Krystal J, Baldwin RM, Seibyl JP, Bowers M et al. Increased striatal dopamine transmission in schizophrenia: confirmation in a second cohort. Am J Psychiatry 1998; 155: 761-767. (Pubitemid 28252654)
14. Lindstrom LH, Gefvert O, Hagberg G, Lundberg T, Bergstrom M, Hartvig P et al. Increased dopamine synthesis rate in medial prefrontal cortex and striatum in schizophrenia indicated by L-(beta-11C) DOPA and PET. Biol Psychiatry 1999; 46: 681-688. (Pubitemid 29401864)
15. Laruelle M, Abi-Dargham A, van Dyck CH, Gil R, D'Souza CD, Erdos J et al. Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects. Proc Natl Acad Sci USA 1996; 93: 9235-9240.
16. Lyon GJ, Abi-Dargham A, Moore H, Lieberman JA, Javitch JA, Sulzer D. Presynaptic regulation of dopamine transmission in schizophrenia. Schizophr Bull 2011; 37: 108-117.
17. Murray RM, Lappin J, Di Forti M. Schizophrenia: from developmental deviance to dopamine dysregulation. Eur Neuropsychopharmacol 2008; 18(Suppl 3): S129-S134.
18. Di Forti M, Lappin JM, Murray RM. Risk factors for schizophrenia-all roads lead to dopamine. Eur Neuropsychopharmacol 2007; 17(Suppl 2): S101-S107.
19. Howes OD, Kapur S. The dopamine hypothesis of schizophrenia: version III-the final common pathway. Schizophr Bull 2009; 35: 549-562.
20. Thompson BL, Levitt P, Stanwood GD. Prenatal exposure to drugs: effects on brain development and implications for policy and education. Nat Rev Neurosci 2009; 10: 303-312.
21. Chang L, Alicata D, Ernst T, Volkow N. Structural and metabolic brain changes in the striatum associated with methamphetamine abuse. Addiction 2007; 102(Suppl 1): 16-32. (Pubitemid 46328220)
22. Chang L, Smith LM, LoPresti C, Yonekura ML, Kuo J, Walot I et al. Smaller subcortical volumes and cognitive deficits in children with prenatal methamphetamine exposure. Psychiatry Res 2004; 132: 95-106. (Pubitemid 39643007)
23. Howes OD, Montgomery AJ, Asselin MC, Murray RM, Valli I, Tabraham P et al. Elevated striatal dopamine function linked to prodromal signs of schizophrenia. Arch Gen Psychiatry 2009; 66: 13-20.
24. Meyer U, Feldon J. Epidemiology-driven neurodevelopmental animal models of schizophrenia. Prog Neurobiol 2010; 90: 285-326.
25. Sams-Dodd F, Lipska BK, Weinberger DR. Neonatal lesions of the rat ventral hippocampus result in hyperlocomotion and deficits in social behaviour in adulthood. Psychopharmacology (Berl) 1997; 132: 303-310. (Pubitemid 27351432)
26. Tseng KY, Chambers RA, Lipska BK. The neonatal ventral hippocampal lesion as a heuristic neurodevelopmental model of schizophrenia. Behav Brain Res 2009; 204: 295-305.
27. Lodge DJ, Behrens MM, Grace AA. A loss of parvalbumin-containing interneurons is associated with diminished oscillatory activity in an animal model of schizophrenia. J Neurosci 2009; 29: 2344-2354.
28. Hoftman GD, Lewis DA. Postnatal developmental trajectories of neural circuits in the primate prefrontal cortex: identifying sensitive periods for vulnerability to schizophrenia. Schizophr Bull 2011; 37: 493-503.
29. O'Donnell P. Adolescent onset of cortical disinhibition in schizophrenia: insights from animal models. Schizophr Bull 2011; 37: 484-492.
30. Boksa P. Animal models of obstetric complications in relation to schizophrenia. Brain Res Brain Res Rev 2004; 45: 1-17. (Pubitemid 38520012)
31. Kellendonk C, Simpson EH, Polan HJ, Malleret G, Vronskaya S, Winiger V et al. Transient and selective overexpression of dopamine D2 receptors in the striatum causes persistent abnormalities in prefrontal cortex functioning. Neuron 2006; 49: 603-615. (Pubitemid 43221894)
32. Slamberova R, Pometlova M, Charousova P. Postnatal development of rat pups is altered by prenatal methamphetamine exposure. Prog Neuropsychopharmacol Biol Psychiatry 2006; 30: 82-88. (Pubitemid 43021325)
33. Brown AS. The environment and susceptibility to schizophrenia. Prog Neurobiol 2011; 93: 23-58.
34. McGrath JJ, Eyles DW, Pedersen CB, Anderson C, Ko P, Burne TH et al. Neonatal vitamin D status and risk of schizophrenia: a population-based case-control study. Arch Gen Psychiatry 2010; 67: 889-894.
35. McGrath J, Saari K, Hakko H, Jokelainen J, Jones P, Jarvelin MR et al. Vitamin D supplementation during the first year of life and risk of schizophrenia: a Finnish birth cohort study. Schizophr Res 2004; 67: 237-245. (Pubitemid 38251454)
36. McGrath JJ, Burne TH, Feron F, Mackay-Sim A, Eyles DW. Developmental vitamin D deficiency and risk of schizophrenia: a 10-year update. Schizophr Bull 2010; 36: 1073-1078.
37. McGrath J. Hypothesis: is low prenatal vitamin D a risk-modifying factor for schizophrenia? Schizophr Res 1999; 40: 173-177.
38. Eyles D, Brown J, Mackay-Sim A, McGrath J, Feron F. Vitamin D3 and brain development. Neuroscience 2003; 118: 641-653.
39. Feron F, Burne TH, Brown J, Smith E, McGrath JJ, Mackay-Sim A et al. Developmental vitamin D3 deficiency alters the adult rat brain. Brain Res Bull 2005; 65: 141-148. (Pubitemid 40348799)
40. Becker A, Eyles DW, McGrath JJ, Grecksch G. Transient prenatal vitamin D deficiency is associated with subtle alterations in learning and memory functions in adult rats. Behav Brain Res 2005; 161: 306-312. (Pubitemid 40732414)
41. Kesby JP, Burne TH, McGrath JJ, Eyles DW. Developmental vitamin D deficiency alters MK 801-induced hyperlocomotion in the adult rat: An animal model of schizophrenia. Biol Psychiatry 2006; 60: 591-596. (Pubitemid 44402370)
42. O'Loan J, Eyles DW, Kesby J, Ko P, McGrath JJ, Burne TH. Vitamin D deficiency during various stages of pregnancy in the rat; its impact on development and behaviour in adult offspring. Psychoneuroendocrinology 2007; 32: 227-234. (Pubitemid 46400276)
43. Kesby JP, Cui X, O'Loan J, McGrath JJ, Burne TH, Eyles DW. Developmental vitamin D deficiency alters dopamine-mediated behaviors and dopamine transporter function in adult female rats. Psychopharmacology (Berl) 2010; 208: 159-168.
44. Becker A, Grecksch G. Pharmacological treatment to augment hole board habituation in prenatal Vitamin D-deficient rats. Behav Brain Res 2006; 166: 177-183. (Pubitemid 41677373)
45. Grecksch G, Ruthrich H, Hollt V, Becker A. Transient prenatal vitamin D deficiency is associated with changes of synaptic plasticity in the dentate gyrus in adult rats. Psychoneuroendocrinology 2009; 34(Suppl 1): S258-S264.
46. Keilhoff G, Grecksch G, Becker A. Haloperidol normalized prenatal vitamin D depletioninduced reduction of hippocampal cell proliferation in adult rats. Neurosci Lett 2010; 476: 94-98.
47. Brown AS. Prenatal infection as a risk factor for schizophrenia. Schizophr Bull 2006; 32: 200-202.
48. Brown AS, Derkits EJ. Prenatal infection and schizophrenia: a review of epidemiologic and translational studies. Am J Psychiatry 2010; 167: 261-280.
49. Meyer U, Feldon J, Fatemi SH. In-vivo rodent models for the experimental investigation of prenatal immune activation effects in neurodevelopmental brain disorders. Neurosci Biobehav Rev 2009; 33: 1061-1079.
50. Meyer U, Knuesel I, Nyffeler M, Feldon J. Chronic clozapine treatment improves prenatal infection-induced working memory deficits without influencing adult hippocampal neurogenesis. Psychopharmacology (Berl) 2010; 208: 531-543.
51. Meyer U, Nyffeler M, Schwendener S, Knuesel I, Yee BK, Feldon J. Relative prenatal and postnatal maternal contributions to schizophrenia-related neurochemical dysfunction after in utero immune challenge. Neuropsychopharmacology 2008; 33: 441-456. (Pubitemid 350243354)
52. Ozawa K, Hashimoto K, Kishimoto T, Shimizu E, Ishikura H, Iyo M. Immune activation during pregnancy in mice leads to dopaminergic hyperfunction and cognitive impairment in the offspring: a neurodevelopmental animal model of schizophrenia. Biol Psychiatry 2006; 59: 546-554. (Pubitemid 43320543)
53. Zuckerman L, Weiner I. Post-pubertal emergence of disrupted latent inhibition following prenatal immune activation. Psychopharmacology (Berl) 2003; 169: 308-313. (Pubitemid 37255519)
54. Vuillermot S, Weber L, Feldon J, Meyer U. A longitudinal examination of the neurodevelopmental impact of prenatal immune activation in mice reveals primary defects in dopaminergic development relevant to schizophrenia. J Neurosci 2010; 30: 1270-1287.
55. Zuckerman L, Weiner I. Maternal immune activation leads to behavioral and pharmacological changes in the adult offspring. J Psychiatr Res 2005; 39: 311-323. (Pubitemid 40255916)
56. Li Q, Cheung C, Wei R, Hui ES, Feldon J, Meyer U et al. Prenatal immune challenge is an environmental risk factor for brain and behavior change relevant to schizophrenia: evidence from MRI in a mouse model. PLoS One 2009; 4: e6354.
57. Piontkewitz Y, Assaf Y, Weiner I. Clozapine administration in adolescence prevents postpubertal emergence of brain structural pathology in an animal model of schizophrenia. Biol Psychiatry 2009; 66: 1038-1046.
58. Meyer U, Nyffeler M, Yee BK, Knuesel I, Feldon J. Adult brain and behavioral pathological markers of prenatal immune challenge during early/middle and late fetal development in mice. Brain Behav Immun 2008; 22: 469-486. (Pubitemid 351451821)
59. Humble MB, Gustafsson S, Bejerot S. Low serum levels of 25-hydroxyvitamin D (25-OHD) among psychiatric out-patients in Sweden: Relations with season, age, ethnic origin and psychiatric diagnosis. J Steroid Biochem Mol Biol 2010; 121: 467-470.
60. Fernell E, Barnevik-Olsson M, Bagenholm G, Gillberg C, Gustafsson S, Saaf M. Serum levels of 25-hydroxyvitamin D in mothers of Swedish and of Somali origin who have children with and without autism. Acta Paediatr 2010; 99: 743-747.
61. Eyles DW. Vitamin D and autism: does skin colour modify risk? Acta Paediatr 2010; 99: 645-647.
62. Enstrom AM, Onore CE, Van de Water JA, Ashwood P. Differential monocyte responses to TLR ligands in children with autism spectrum disorders. Brain Behav Immun 2010; 24: 64-71.
63. Shi L, Smith SE, Malkova N, Tse D, Su Y, Patterson PH. Activation of the maternal immune system alters cerebellar development in the offspring. Brain Behav Immun 2009; 23: 116-123.
64. Baksi SN, Hughes MJ. Chronic vitamin D deficiency in the weanling rat alters catecholamine metabolism in the cortex. Brain Res 1982; 242: 387-390.
65. Tenenhouse A, Warner M, Commissiong JW. Neurotransmitters in the CNS of the vitamin D deficient, hypocalcemic rat. Neurochem Int 1991; 18: 249-255.
66. Matkovits T, Christakos S. Ligand occupancy is not required for vitamin D receptor and retinoid receptor-mediated transcriptional activation. Mol Endocrinol 1995; 9: 232-242.
67. Eyles DW, Smith S, Kinobe R, Hewison M, McGrath JJ. Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain. J Chem Neuroanat 2005; 29: 21-30. (Pubitemid 39602785)
68. Burne TH, Becker A, Brown J, Eyles DW, Mackay-Sim A, McGrath JJ. Transient prenatal Vitamin D deficiency is associated with hyperlocomotion in adult rats. Behav Brain Res 2004; 154: 549-555. (Pubitemid 39094006)
69. Eyles DW, Rogers F, Buller K, McGrath JJ, Ko P, French K et al. Developmental vitamin D (DVD) deficiency in the rat alters adult behaviour independently of HPA function. Psychoneuroendocrinology 2006; 31: 958-964. (Pubitemid 44148913)
70. Smith MP, Fletcher-Turner A, Yurek DM, Cass WA. Calcitriol protection against dopamine loss induced by intracerebroventricular administration of 6-hydroxydopamine. Neurochem Res 2006; 31: 533-539. (Pubitemid 43873748)
71. Tekes K, Gyenge M, Folyovich A, Csaba G. Influence of neonatal vitamin A or vitamin D treatment on the concentration of biogenic amines and their metabolites in the adult rat brain. Horm Metab Res 2009; 41: 277-280.
72. Meyer U, Feldon J. Prenatal exposure to infection: a primary mechanism for abnormal dopaminergic development in schizophrenia. Psychopharmacology (Berl) 2009; 206: 587-602.
73. Roberts RC, Roche JK, Conley RR, Lahti AC. Dopaminergic synapses in the caudate of subjects with schizophrenia: relationship to treatment response. Synapse 2009; 63: 520-530.
74. Winter C, Djodari-Irani A, Sohr R, Morgenstern R, Feldon J, Juckel G et al. Prenatal immune activation leads to multiple changes in basal neurotransmitter levels in the adult brain: implications for brain disorders of neurodevelopmental origin such as schizophrenia. Int J Neuropsychopharmacol 2009; 12: 513-524.
75. Carpenter WT, Koenig JI. The evolution of drug development in schizophrenia: past issues and future opportunities. Neuropsychopharmacology 2008; 33: 2061-2079. (Pubitemid 351992095)
76. Veenstra TD, Prufer K, Koenigsberger C, Brimijoin SW, Grande JP, Kumar R. 1,25-Dihydroxyvitamin D3 receptors in the central nervous system of the rat embryo. Brain Res 1998; 804: 193-205. (Pubitemid 28496623)
77. Gates MA, Torres EM, White A, Fricker-Gates RA, Dunnett SB. Re-examining the ontogeny of substantia nigra dopamine neurons. Eur J Neurosci 2006; 23: 1384-1390.
78. Smidt MP, Burbach JP. How to make a mesodiencephalic dopaminergic neuron. Nat Rev Neurosci 2007; 8: 21-32. (Pubitemid 46011996)
79. Cui X, Pelekanos M, Burne TH, McGrath JJ, Eyles DW. Maternal vitamin D deficiency alters the expression of genes involved in dopamine specification in the developing rat mesencephalon. Neurosci Lett 2010; 486: 220-223.
80. Kesby JP, Cui X, Ko P, McGrath JJ, Burne TH, Eyles DW. Developmental vitamin D deficiency alters dopamine turnover in neonatal rat forebrain. Neurosci Lett 2009; 461: 155-158.
81. Bayer SA, Wills KV, Triarhou LC, Ghetti B. Time of neuron origin and gradients of neurogenesis in midbrain dopaminergic neurons in the mouse. Exp Brain Res 1995; 105: 191-199.
82. Prakash N, Wurst W. Development of dopaminergic neurons in the mammalian brain. Cell Mol Life Sci 2006; 63: 187-206. (Pubitemid 43100289)
83. Meyer U, Engler A, Weber L, Schedlowski M, Feldon J. Preliminary evidence for a modulation of fetal dopaminergic development by maternal immune activation during pregnancy. Neuroscience 2008; 154: 701-709.
84. Puchacz E, Stumpf WE, Stachowiak EK, Stachowiak MK. Vitamin D increases expression of the tyrosine hydroxylase gene in adrenal medullary cells. Brain Res Mol Brain Res 1996; 36: 193-196. (Pubitemid 26058893)
85. Sanchez B, Relova JL, Gallego R, Ben-Batalla I, Perez-Fernandez R. 1,25-Dihydroxyvitamin D3 administration to 6-hydroxydopamine-lesioned rats increases glial cell line-derived neurotrophic factor and partially restores tyrosine hydroxylase expression in substantia nigra and striatum. J Neurosci Res 2009; 87: 723-732.
86. Wang JY, Wu JN, Cherng TL, Hoffer BJ, Chen HH, Borlongan CV et al. Vitamin D-3 attenuates 6-hydroxydopamine-induced neurotoxicity in rats. Brain Res 2001; 904: 67-75. (Pubitemid 32545355)
87. Chen KB, Lin AM, Chiu TH. Systemic vitamin D3 attenuated oxidative injuries in the locus coeruleus of rat brain. Ann NY Acad Sci 2003; 993: 313-324, discussion 345-319. (Pubitemid 36808460)
88. Naveilhan P, Neveu I, Wion D, Brachet P. 1,25-Dihydroxyvitamin D3, an inducer of glial cell line-derived neurotrophic factor. Neuroreport 1996; 7: 2171-2175. (Pubitemid 26361840)
89. Salvatore MF, Zhang JL, Large DM, Wilson PE, Gash CR, Thomas TC et al. Striatal GDNF administration increases tyrosine hydroxylase phosphorylation in the rat striatum and substantia nigra. J Neurochem 2004; 90: 245-254. (Pubitemid 38879178)
90. Meyer U, Nyffeler M, Engler A, Urwyler A, Schedlowski M, Knuesel I et al. The time of prenatal immune challenge determines the specificity of inflammation-mediated brain and behavioral pathology. J Neurosci 2006; 26: 4752-4762. (Pubitemid 44315314)
91. Ling ZD, Potter ED, Lipton JW, Carvey PM. Differentiation of mesencephalic progenitor cells into dopaminergic neurons by cytokines. Exp Neurol 1998; 149: 411-423. (Pubitemid 28115079)
92. Potter ED, Ling ZD, Carvey PM. Cytokine-induced conversion of mesencephalic-derived progenitor cells into dopamine neurons. Cell Tissue Res 1999; 296: 235-246. (Pubitemid 29219176)
93. Carvey PM, Ling ZD, Sortwell CE, Pitzer MR, McGuire SO, Storch A et al. A clonal line of mesencephalic progenitor cells converted to dopamine neurons by hematopoietic cytokines: a source of cells for transplantation in Parkinson's disease. Exp Neurol 2001; 171: 98-108. (Pubitemid 32848448)
94. Akaneya Y, Takahashi M, Hatanaka H. Interleukin-1 beta enhances survival and interleukin-6 protects against MPP+ neurotoxicity in cultures of fetal rat dopaminergic neurons. Exp Neurol 1995; 136: 44-52.
95. Zhu G, Mehler MF, Mabie PC, Kessler JA. Developmental changes in progenitor cell responsiveness to cytokines. J Neurosci Res 1999; 56: 131-145. (Pubitemid 29201052)
96. Doherty GH. Developmental switch in the effects of TNFalpha on ventral midbrain dopaminergic neurons. Neurosci Res 2007; 57: 296-305. (Pubitemid 46188485)
97. Jarskog LF, Xiao H, Wilkie MB, Lauder JM, Gilmore JH. Cytokine regulation of embryonic rat dopamine and serotonin neuronal survival in vitro. Int J Dev Neurosci 1997; 15: 711-716. (Pubitemid 27478191)
98. Mehta RG, Mehta RR. Vitamin D and cancer. J Nutr Biochem 2002; 13: 252-264. (Pubitemid 34556686)
99. Meyer U, Yee BK, Feldon J. The neurodevelopmental impact of prenatal infections at different times of pregnancy: the earlier the worse? Neuroscientist 2007; 13: 241-256. (Pubitemid 46801755)
100. Ko P, Burkert R, McGrath J, Eyles D. Maternal vitamin D3 deprivation and the regulation of apoptosis and cell cycle during rat brain development. Brain Res Dev Brain Res 2004; 153: 61-68. (Pubitemid 39298877)
101. Cui X, McGrath JJ, Burne TH, Mackay-Sim A, Eyles DW. Maternal vitamin D depletion alters neurogenesis in the developing rat brain. Int J Dev Neurosci 2007; 25: 227-232. (Pubitemid 46818858)
102. Brown J, Bianco JI, McGrath JJ, Eyles DW. 1,25-Dihydroxyvitamin D3 induces nerve growth factor, promotes neurite outgrowth and inhibits mitosis in embryonic rat hippocampal neurons. Neurosci Lett 2003; 343: 139-143. (Pubitemid 36577534)
103. Joseph B, Wallen-Mackenzie A, Benoit G, Murata T, Joodmardi E, Okret S et al. p57(Kip2) cooperates with Nurr1 in developing dopamine cells. Proc Natl Acad Sci USA 2003; 100: 15619-15624. (Pubitemid 38021039)
104. Wallen A, Zetterstrom RH, Solomin L, Arvidsson M, Olson L, Perlmann T. Fate of mesencephalic AHD2-expressing dopamine progenitor cells in NURR1 mutant mice. Exp Cell Res 1999; 253: 737-746. (Pubitemid 30003136)
105. Kawata H, Kamiakito T, Takayashiki N, Tanaka A. Vitamin D3 suppresses the androgenstimulated growth of mouse mammary carcinoma SC-3 cells by transcriptional repression of fibroblast growth factor 8. J Cell Physiol 2006; 207: 793-799. (Pubitemid 43668244)
106. Nyffeler M, Meyer U, Yee BK, Feldon J, Knuesel I. Maternal immune activation during pregnancy increases limbic GABAA receptor immunoreactivity in the adult offspring: implications for schizophrenia. Neuroscience 2006; 143: 51-62. (Pubitemid 44667305)
107. Klafke R, Wurst W, Prakash N. Genetic control of rodent midbrain dopaminergic neuron development in the light of human disease. Pharmacopsychiatry 2008; 41(Suppl 1): S44-S50.
108. Wallen AA, Castro DS, Zetterstrom RH, Karlen M, Olson L, Ericson J et al. Orphan nuclear receptor Nurr1 is essential for Ret expression in midbrain dopamine neurons and in the brain stem. Mol Cell Neurosci 2001; 18: 649-663. (Pubitemid 34060146)
109. Zetterstrom RH, Solomin L, Jansson L, Hoffer BJ, Olson L, Perlmann T. Dopamine neuron agenesis in Nurr1-deficient mice. Science 1997; 276: 248-250. (Pubitemid 27172681)
110. 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.
111. Jiang C, Wan X, He Y, Pan T, Jankovic J, Le W. Age-dependent dopaminergic dysfunction in Nurr1 knockout mice. Exp Neurol 2005; 191: 154-162. (Pubitemid 39612401)
112. Solberg Y, Silverman WF, Pollack Y. Prenatal ontogeny of tyrosine hydroxylase gene expression in the rat ventral mesencephalon. Brain Res Dev Brain Res 1993; 73: 91-97. (Pubitemid 23144610)
113. Smidt MP, van Schaick HS, Lanctot C, Tremblay JJ, Cox JJ, van der Kleij AA et al. A homeodomain gene Ptx3 has highly restricted brain expression in mesencephalic dopaminergic neurons. Proc Natl Acad Sci USA 1997; 94: 13305-13310. (Pubitemid 27518517)
114. Martinat C, Bacci JJ, Leete T, Kim J, Vanti WB, Newman AH et al. Cooperative transcription activation by Nurr1 and Pitx3 induces embryonic stem cell maturation to the midbrain dopamine neuron phenotype. Proc Natl Acad Sci USA 2006; 103: 2874-2879.
115. Backman C, You ZB, Perlmann T, Hoffer BJ. Elevated locomotor activity without altered striatal dopamine contents in Nurr1 heterozygous mice after acute exposure to methamphetamine. Behav Brain Res 2003; 143: 95-100. (Pubitemid 36802188)
116. Eells JB, Lipska BK, Yeung SK, Misler JA, Nikodem VM. Nurr1-null heterozygous mice have reduced mesolimbic and mesocortical dopamine levels and increased stressinduced locomotor activity. Behav Brain Res 2002; 136: 267-275. (Pubitemid 35246412)
117. 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. (Pubitemid 47172691)
118. Xing G, Zhang L, Russell S, Post R. Reduction of dopamine-related transcription factors Nurr1 and NGFI-B in the prefrontal cortex in schizophrenia and bipolar disorders. Schizophr Res 2006; 84: 36-56.
119. Bergman O, Westberg L, Nilsson LG, Adolfsson R, Eriksson E. Preliminary evidence that polymorphisms in dopamine-related transcription factors LMX1A, LMX1B and PITX3 are associated with schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2010; 34: 1094-1097.
120. Ardayfio PA, Leung A, Park J, Hwang DY, Moran-Gates T, Choi YK et al. Pitx3-deficient aphakia mice display unique behavioral responses to psychostimulant and antipsychotic drugs. Neuroscience 2010; 166: 391-396.
121. Pletnikov MV. Inducible and conditional transgenic mouse models of schizophrenia. Prog Brain Res 2009; 179: 35-47.
122. Kubo K, Tomita K, Uto A, Kuroda K, Seshadri S, Cohen J et al. Migration defects by DISC1 knockdown in C57BL/6, 129X1/SvJ, and ICR strains via in utero gene transfer and virus-mediated RNAi. Biochem Biophys Res Commun 2010; 400: 631-637.
123. Burnet PW, Anderson PN, Chen L, Nikiforova N, Harrison PJ, Wood MJ. D-amino acid oxidase knockdown in the mouse cerebellum reduces NR2A mRNA. Mol Cell Neurosci 2011; 46: 167-175.
124. Blin M, Norton W, Bally-Cuif L, Vernier P. NR4A2 controls the differentiation of selective dopaminergic nuclei in the zebrafish brain. Mol Cell Neurosci 2008; 39: 592-604.
125. Furukubo-Tokunaga K.Modeling schizophrenia in flies Prog Brain Res 2009,179:107-115.
126. Burne T, Scott E, van Swinderen B, Hilliard M, Reinhard J, Claudianos C et al. Big ideas for small brains: what can psychiatry learn from worms, flies, bees and fish? Mol Psychiatry 2011; 16: 7-16.
127. White JH. Vitamin D signaling, infectious diseases, and regulation of innate immunity. Infect Immun 2008; 76: 3837-3843.
128. Cantorna MT. Vitamin D and its role in immunology: multiple sclerosis, and inflammatory bowel disease. Prog Biophys Mol Biol 2006; 92: 60-64. (Pubitemid 43831951)
129. Murillo G, Nagpal V, Tiwari N, Benya RV, Mehta RG. Actions of vitamin D are mediated by the TLR4 pathway in inflammation-induced colon cancer. J Steroid Biochem Mol Biol 2010; 121: 403-407.
130. Garcion E, Sindji L, Montero-Menei C, Andre C, Brachet P, Darcy F. Expression of inducible nitric oxide synthase during rat brain inflammation: regulation by 1,25-dihydroxyvitamin D3. Glia 1998; 22: 282-294. (Pubitemid 28159019)
131. Pantelis C, Velakoulis D, McGorry PD, Wood SJ, Suckling J, Phillips LJ et al. Neuroanatomical abnormalities before and after onset of psychosis: a cross-sectional and longitudinal MRI comparison. Lancet 2003; 361: 281-288. (Pubitemid 36126187)
132. Konig J. Animal models of schizophrenia. Available from: http://www.schizophreniaforum.org/res/models/default.asp, 2009 Accessed Date 2009.