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Psychoneuroimmunology pp 259–285Cite as

The MRL Model: A Valuable Tool in Studies of Autoimmunity-Brain Interactions

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 1781))

Abstract

The link between systemic autoimmunity, brain pathology, and aberrant behavior is still a largely unexplored field of biomedical science. Accumulating evidence points to causal relationships between immune factors, neurodegeneration, and neuropsychiatric manifestations. By documenting autoimmunity-associated neuronal degeneration and cytotoxicity of the cerebrospinal fluid from disease-affected subjects, the murine MRL model had shown high validity in revealing principal pathogenic circuits. In addition, unlike any other autoimmune strain, MRL mice produce antibodies commonly found in patients suffering from lupus and other autoimmune disorders. This review highlights importance of the MRL model as a useful preparation in understanding the links between immune system and brain function.

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References

  1. Ader R, Felten D, Cohen N (2001) Psychoneuroimmunology, vol 1-2, 3rd edn. Academic Press, New York

    Google Scholar 

  2. Goehler LE, Gaykema RP, Hansen MK, Anderson K, Maier SF, Watkins LR (2000) Vagal immune-to-brain communication: a visceral chemosensory pathway. Auton Neurosci 85(1–3):49–59

    Article  CAS  PubMed  Google Scholar 

  3. Benveniste EN, Huneycutt BS, Shrikant P, Ballestas ME (1995) Second messenger systems in the regulation of cytokines and adhesion molecules in the central nervous system. Brain Behav Immun 9:304–314

    Article  CAS  PubMed  Google Scholar 

  4. Dunn AJ (2000) Cytokine activation of the HPA axis. Ann N Y Acad Sci 917:608–617

    Article  CAS  PubMed  Google Scholar 

  5. McEwen BS (2000) Allostasis and allostatic load: implications for neuropsychopharmacology. Neuropsychopharmacology 22(2):108–124

    Article  CAS  PubMed  Google Scholar 

  6. Johnson EO, Kamilaris TC, Chrousos GP, Gold PW (1992) Mechanisms of stress: a dynamic overview of hormonal and behavioral homeostasis. Neurosci Biobehav Rev 16:115–130

    Article  CAS  PubMed  Google Scholar 

  7. Dantzer R, O'Connor JC, Freund GG, Johnson RW, Kelley KW (2008) From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 9(1):46–56

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. McEwen BS (2003) Mood disorders and allostatic load. Biol Psychiatry 54(3):200–207

    Article  PubMed  Google Scholar 

  9. McEwen BS, Biron CA, Brunson KW, Bulloch K, Chambers WH, Dhabhar FS, Goldfarb RH, Kitson RP, Miller AH, Spencer RL, Weiss JM (1997) The role of adrenocorticoids as modulators of immune function in health and disease: neural, endocrine and immune interactions. Brain Res Rev 23(1–2):79–133

    Article  CAS  PubMed  Google Scholar 

  10. Cotman CW, Brinton RE, Galaburda A, McEwen B, Schneider DM (1987) The neuro-immune-endocrine connection. Raven Press, New York

    Google Scholar 

  11. Kapadia M, Sakic B (2011) Autoimmune and inflammatory mechanisms of CNS damage. Prog Neurobiol 95(3):301–333

    Article  CAS  PubMed  Google Scholar 

  12. Hanly JG (2005) Neuropsychiatric lupus. Rheum Dis Clin North Am 31(2):273–298

    Article  PubMed  Google Scholar 

  13. Tincani A, Brey R, Balestrieri G, Vitali C, Doria A, Galeazzi M, Meroni PL, Migliorini P, Neri R, Tavoni A, Bombardieri S (1996) International survey on the management of patients with SLE .2. The results of a questionnaire regarding neuropsychiatric manifestations. Clin Exp Rheumatol 14(Suppl. 16):S23–S29

    PubMed  Google Scholar 

  14. van Dam AP, Wekking EM, Oomen HA (1991) Psychiatric symptoms as features of systemic lupus erythematosus. Psychother Psychosom 55(2–4):132–140

    PubMed  Google Scholar 

  15. Colamussi P, Giganti M, Cittanti C, Dovigo L, Trotta F, Tola MR, Tamarozzi R, Lucignani G, Piffanelli A (1995) Brain single-photon emission tomography with Tc-99m-HMPAO in neuropsychiatric systemic lupus erythematosus: relations with EEG and MRI findings and clinical manifestations. Eur J Nucl Med 22:17–24

    Article  CAS  PubMed  Google Scholar 

  16. Handa R, Sahota P, Kumar M, Jagannathan NR, Bal CS, Gulati M, Tripathi BM, Wali JP (2003) In vivo proton magnetic resonance spectroscopy (MRS) and single photon emission computerized tomography (SPECT) in systemic lupus erythematosus (SLE). Magn Reson Imaging 21(9):1033–1037

    Article  CAS  PubMed  Google Scholar 

  17. Huang WS, Chiu PY, Tsai CH, Kao A, Lee CC (2002) Objective evidence of abnormal regional cerebral blood flow in patients with systemic lupus erythematosus on Tc-99m ECD brain SPECT. Rheumatol Int 22(5):178–181

    Article  CAS  PubMed  Google Scholar 

  18. Lopez-Longo FJ, Carol N, Almoguera MI, Olazaran J, onso-Farto JC, Ortega A, Monteagudo I, Gonzalez CM, Carreno L (2003) Cerebral hypoperfusion detected by SPECT in patients with systemic lupus erythematosus is related to clinical activity and cumulative tissue damage. Lupus 12(11):813–819

    Article  CAS  PubMed  Google Scholar 

  19. Komatsu N, Kodama K, Yamanouchi N, Okada S, Noda S, Nawata Y, Takabayashi K, Iwamoto I, Saito Y, Uchida Y, Ito H, Yoshikawa K, Sato T (1999) Decreased regional cerebral metabolic rate for glucose in systemic lupus erythematosus patients with psychiatric symptoms. Eur Neurol 42(1):41–48

    Article  CAS  PubMed  Google Scholar 

  20. Brooks WM, Sabet A, Sibbitt WL, Barker PB, van Zijl PC, Duyn JH, Moonen CT (1997) Neurochemistry of brain lesions determined by spectroscopic imaging in systemic lupus erythematosus. J Rheumatol 24(12):2323–2329

    CAS  PubMed  Google Scholar 

  21. Volkow ND, Warner N, McIntyre R, Valentine A, Kulkarni M, Mullani N, Gould L (1988) Cerebral involvement in systemic lupus erythematosus. Am J Physiol Imaging 3(2):91–98

    CAS  PubMed  Google Scholar 

  22. Gonzalez-Scarano F, Lisak RP, Bilaniuk LT, Zimmerman RA, Atkins PC, Zweiman B (1979) Cranial computed tomography in the diagnosis of systemic lupus erythematosus. Ann Neurol 5(2):158–165

    Article  CAS  PubMed  Google Scholar 

  23. Kaell AT, Shetty M, Lee BC, Lockshin MD (1986) The diversity of neurologic events in systemic lupus erythematosus. Prospective clinical and computed tomographic classification of 82 events in 71 patients. Arch Neurol 43(3):273–276

    Article  CAS  PubMed  Google Scholar 

  24. Miguel EC, Pereira RM, Pereira CA, Baer L, Gomes RE, de Sa LC, Hirsch R, de Barros NG, de Navarro JM, Gentil V (1994) Psychiatric manifestations of systemic lupus erythematosus: clinical features, symptoms, and signs of central nervous system activity in 43 patients. Medicine 73(4):224–232

    Article  CAS  PubMed  Google Scholar 

  25. Omdal R, Selseth B, Klow NE, Husby G, Mellgren SI (1989) Clinical neurological, electrophysiological, and cerebral CT scan findings in systemic lupus erythematosus. Scand J Rheumatol 18(5):283–289

    Article  CAS  PubMed  Google Scholar 

  26. Ainiala H, Dastidar P, Loukkola J, Lehtimaki T, Korpela M, Peltola J, Hietaharju A (2005) Cerebral MRI abnormalities and their association with neuropsychiatric manifestations in SLE: a population-based study. Scand J Rheumatol 34(5):376–382

    Article  CAS  PubMed  Google Scholar 

  27. Waterloo K, Omdal R, Jacobsen EA, Klow NE, Husby G, Torbergsen T, Mellgren SI (1999) Cerebral computed tomography and electroencephalography compared with neuropsychological findings in systemic lupus erythematosus. J Neurol 246(8):706–711

    Article  CAS  PubMed  Google Scholar 

  28. Sibbitt WL, Sibbitt RR (1993) Magnetic resonance spectroscopy and positron emission tomography scanning in neuropsychiatric systemic lupus erythematosus. Rheum Dis Clin North Am 19(4):851–868

    PubMed  Google Scholar 

  29. Sibbitt WL, Haseler LJ, Griffey RH, Hart BL, Sibbitt RR, Matwiyoff NA (1994) Analysis of cerebral structural changes in systemic lupus erythematosus by proton MR spectroscopy. AJNR Am J Neuroradiol 15:923–928

    PubMed  Google Scholar 

  30. Jennekens FG, Kater L (2002) The central nervous system in systemic lupus erythematosus. Part 2. Pathogenetic mechanisms of clinical syndromes: a literature investigation. Rheumatology (Oxford) 41(6):619–630

    Article  CAS  Google Scholar 

  31. McLean BN, Miller D, Thompson EJ (1995) Oligoclonal banding of IgG in CSF, blood-brain barrier function, and MRI findings in patients with sarcoidosis, systemic lupus erythematosus, and Behcet's disease involving the nervous system. J Neurol Neurosurg Psychiatry 58(5):548–554

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Hirohata S, Hirose S, Miyamoto T (1985) Cerebrospinal fluid IgM, IgA, and IgG indexes in systemic lupus erythematosus. Their use as estimates of central nervous system disease activity. Arch Intern Med 145(10):1843–1846

    Article  CAS  PubMed  Google Scholar 

  33. Winfield JB, Shaw M, Silverman LM, Eisenberg RA, Wilson HA III, Koffler D (1983) Intrathecal IgG synthesis and blood-brain barrier impairment in patients with systemic lupus erythematosus and central nervous system dysfunction. Am J Med 74(5):837–844

    Article  CAS  PubMed  Google Scholar 

  34. Yoshio T, Hirata D, Onda K, Nara H, Minota S (2005) Antiribosomal P protein antibodies in cerebrospinal fluid are associated with neuropsychiatric systemic lupus erythematosus. J Rheumatol 32(1):34–39

    CAS  PubMed  Google Scholar 

  35. Greenwood DL, Gitlits VM, Alderuccio F, Sentry JW, Toh BH (2002) Autoantibodies in neuropsychiatric lupus. Autoimmunity 35(2):79–86

    Article  CAS  PubMed  Google Scholar 

  36. Henn FA, McKinney WT (1987) Animal models in psychiatry. In: Meltzer HY (ed) Psychopharmacology: the third generation of progress. Raven Press, New York, pp 687–695

    Google Scholar 

  37. Dixon FJ, Andrews BS, Eisenberg RA, McConahey PJ, Theofilopoulos AN, Wilson CB (1978) Etiology and pathogenesis of a spontaneous lupus-like syndrome in mice. Arthritis Rheum 21:S64–S67

    Article  CAS  PubMed  Google Scholar 

  38. Szechtman H, Sakic B, Denburg JA (1997) Behaviour of MRL mice: an animal model of disturbed behaviour in systemic autoimmune disease. Lupus 6(3):223–229

    Article  CAS  PubMed  Google Scholar 

  39. Sakic B, Szechtman H, Denburg JA (1997) Neurobehavioral alteration in autoimmune mice. Neurosci Biobehav Rev 21(3):327–340

    Article  CAS  PubMed  Google Scholar 

  40. Alexander JJ, Quigg RJ (2007) Systemic lupus erythematosus and the brain: what mice are telling us. Neurochem Int 50(1):5–11

    Article  CAS  PubMed  Google Scholar 

  41. Sherman GF, Galaburda AM, Behan PO, Rosen GD (1987) Neuroanatomical anomalies in autoimmune mice. Acta Neuropathol (Berl ) 74:239–242

    Article  CAS  Google Scholar 

  42. Theofilopoulos AN (1992) Murine models of lupus. In: Lahita RG (ed) Systemic lupus erythematosus, 2nd edn. Churchill Livingstone, New York, pp 121–194

    Google Scholar 

  43. Andrews BS, Eisenberg RA, Theofilopoulos AN, Izui S, Wilson CB, McConahey PJ, Murphy ED, Roths JB, Dixon FJ (1978) Spontaneous murine lupus-like syndromes. Clinical and immunopathological manifestations in several strains. J Exp Med 148:1198–1215

    Article  CAS  PubMed  Google Scholar 

  44. Gulinello M, Putterman C (2011) The MRL/lpr mouse strain as a model for neuropsychiatric systemic lupus erythematosus. J Biomed Biotechnol 2011:207504

    Article  PubMed  PubMed Central  Google Scholar 

  45. Jeltsch-David H, Muller S (2014) Neuropsychiatric systemic lupus erythematosus and cognitive dysfunction: the MRL-lpr mouse strain as a model. Autoimmun Rev 13(9):963–973. https://doi.org/10.1016/j.autrev.2014.08.015

    Article  PubMed  Google Scholar 

  46. Watanabe-Fukunaga R, Brannan CI, Copeland NG, Jenkins NA, Nagata S (1992) Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature 356:314–317

    Article  CAS  PubMed  Google Scholar 

  47. Nagata S (1994) Mutations in the Fas antigen gene in lpr mice. Semin Immunol 6(1):3–8

    Article  CAS  PubMed  Google Scholar 

  48. Singer GG, Carrera AC, Marshakrothstein A, Martineza C, Abbas AK (1994) Apoptosis, fas and systemic autoimmunity: the MRL-Ipr/Ipr model. Curr Opin Immunol 6:913–920

    Article  CAS  PubMed  Google Scholar 

  49. Park C, Sakamaki K, Tachibana O, Yamashima T, Yamashita J, Yonehara S (1998) Expression of Fas antigen in the normal mouse brain. Biochem Biophys Res Commun 252(3):623–628

    Article  CAS  PubMed  Google Scholar 

  50. Sakic B, Kolb B, Whishaw IQ, Gorny G, Szechtman H, Denburg JA (2000) Immunosuppression prevents neuronal atrophy in lupus-prone mice: evidence for brain damage induced by autoimmune disease? J Neuroimmunol 111(1–2):93–101

    Article  CAS  PubMed  Google Scholar 

  51. Sakic B, Denburg JA, Denburg SD, Szechtman H (1996) Blunted sensitivity to sucrose in autoimmune MRL-lpr mice: a curve-shift study. Brain Res Bull 41(5):305–311

    Article  CAS  PubMed  Google Scholar 

  52. Sakic B, Szechtman H, Denburg SD, Denburg JA (1995) Immunosuppressive treatment prevents behavioral deficit in autoimmune MRL-lpr mice. Physiol Behav 58(4):797–802

    Article  CAS  PubMed  Google Scholar 

  53. Ballok DA, Woulfe J, Sur M, Cyr M, Sakic B (2004) Hippocampal damage in mouse and human forms of systemic autoimmune disease. Hippocampus 14(5):649–661

    Article  PubMed  PubMed Central  Google Scholar 

  54. Williams S, Sakic B, Hoffman SA (2010) Circulating brain-reactive autoantibodies and behavioral deficits in the MRL model of CNS lupus. J Neuroimmunol 218(1–2):73–82

    Article  CAS  PubMed  Google Scholar 

  55. Ballok DA (2007) Neuroimmunopathology in a murine model of neuropsychiatric lupus. Brain Res Rev 54(1):67–79

    Article  CAS  PubMed  Google Scholar 

  56. Sakic B, Szechtman H, Talangbayan H, Denburg SD, Carbotte RM, Denburg JA (1994) Disturbed emotionality in autoimmune MRL-lpr mice. Physiol Behav 56(3):609–617

    Article  CAS  PubMed  Google Scholar 

  57. Sakic B, Szechtman H, Denburg S, Carbotte R, Denburg JA (1993) Emotionality in lupus-prone mice: relationships to autoimmunity. Annual Research Day, Dept. of Biomedical Sciences, McMaster University

    Google Scholar 

  58. Sakic B, Szechtman H, Keffer M, Talangbayan H, Stead R, Denburg JA (1992) A behavioral profile of autoimmune lupus-prone MRL mice. Brain Behav Immun 6:265–285

    Article  CAS  PubMed  Google Scholar 

  59. Ballok DA, Szechtman H, Sakic B (2003) Taste responsiveness and diet preference in autoimmune MRL mice. Behav Brain Res 140(1–2):119–130

    Article  PubMed  Google Scholar 

  60. Sakic B, Gurunlian L, Denburg SD (1998) Reduced aggressiveness and low testosterone levels in autoimmune MRL-lpr males. Physiol Behav 63(2):305–309

    Article  CAS  PubMed  Google Scholar 

  61. Sakic B, Szechtman H, Denburg SD, Carbotte RM, Denburg JA (1993) Spatial learning during the course of autoimmune disease in MRL mice. Behav Brain Res 54:57–66

    Article  CAS  PubMed  Google Scholar 

  62. Hess DC, Taormina M, Thompson J, Sethi KD, Diamond B, Rao R, Feldman DS (1993) Cognitive and neurologic deficits in the MRL/lpr mouse: a clinicopathologic study. J Rheumatol 20:610–617

    CAS  PubMed  Google Scholar 

  63. Brey RL, Amato AA, Kagan-Hallet K, Rhine CB, Stallworth CL (1997) Anti-intercellular adhesion molecule-1 (ICAM-1) antibody treatment prevents central and peripheral nervous system disease in autoimmune-prone mice. Lupus 6(8):645–651

    Article  CAS  PubMed  Google Scholar 

  64. Sakic B, Szechtman H, Stead R, Denburg JA (1996) Joint pathology and behavioral performance in autoimmune MRL-lpr mice. Physiol Behav 60(3):901–905

    Article  CAS  PubMed  Google Scholar 

  65. Abbott NJ, Mendonca LL, Dolman DE (2003) The blood-brain barrier in systemic lupus erythematosus. Lupus 12(12):908–915

    Article  CAS  PubMed  Google Scholar 

  66. Diamond B (2010) Antibodies and the brain: lessons from lupus. J Immunol 185(5):2637–2640

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Vogelweid CM, Johnson GC, Besch-Williford CL, Basler J, Walker SE (1991) Inflammatory central nervous system disease in lupus-prone MRL/lpr mice: comparative histologic and immunohistochemical findings. J Neuroimmunol 35:89–99

    Article  CAS  PubMed  Google Scholar 

  68. Sidor MM, Sakic B, Malinowski PM, Ballok DA, Oleschuk CJ, Macri J (2005) Elevated immunoglobulin levels in the cerebrospinal fluid from lupus-prone mice. J Neuroimmunol 165(1–2):104–113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Alexander EL, Murphy ED, Roths JB, Alexander GE (1983) Congenic autoimmune murine models of central nervous system disease in connective tissue disorders. Ann Neurol 14:242–248

    Article  CAS  PubMed  Google Scholar 

  70. Farrell M, Sakic B, Szechtman H, Denburg JA (1997) Effect of cyclophosphamide on leucocytic infiltration in the brain of MRL/lpr mice. Lupus 6(3):268–274

    Article  CAS  PubMed  Google Scholar 

  71. Ma X, Foster J, Sakic B (2006) Distribution and prevalence of leukocyte phenotypes in brains of lupus-prone mice. J Neuroimmunol 179(1–2):26–36

    Article  CAS  PubMed  Google Scholar 

  72. McHale JF, Harari OA, Marshall D, Haskard DO (1999) TNF-alpha and IL-1 sequentially induce endothelial ICAM-1 and VCAM-1 expression in MRL/lpr lupus-prone mice. J Immunol 163(7):3993–4000

    CAS  PubMed  Google Scholar 

  73. Zameer A, Hoffman SA (2003) Increased ICAM-1 and VCAM-1 expression in the brains of autoimmune mice. J Neuroimmunol 142(1–2):67–74

    Article  CAS  PubMed  Google Scholar 

  74. Tomita M, Holman BJ, Williams LS, Pang KC, Santoro TJ (2001) Cerebellar dysfunction is associated with overexpression of proinflammatory cytokine genes in lupus. J Neurosci Res 64(1):26–33

    Article  CAS  PubMed  Google Scholar 

  75. Tomita M, Holman BJ, Santoro TJ (2001) Aberrant cytokine gene expression in the hippocampus in murine systemic lupus erythematosus. Neurosci Lett 302(2–3):129–132

    Article  CAS  PubMed  Google Scholar 

  76. Alexander JJ, Jacob A, Bao L, Macdonald RL, Quigg RJ (2005) Complement-dependent apoptosis and inflammatory gene changes in murine lupus cerebritis. J Immunol 175(12):8312–8319

    Article  CAS  PubMed  Google Scholar 

  77. McIntyre KR, Ayer-LeLievre C, Persson H (1990) Class II major histocompatibility complex (MHC) gene expression in the mouse brain is elevated in the autoimmune MRL/Mp-lpr/lpr strain. J Neuroimmunol 28:39–52

    Article  CAS  PubMed  Google Scholar 

  78. Ballok DA, Ma X, Denburg JA, Arsenault L, Sakic B (2006) Ibuprofen fails to prevent brain pathology in a model of neuropsychiatric lupus. J Rheumatol 33(11):2199–2213

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Ballok DA, Millward JM, Sakic B (2003) Neurodegeneration in autoimmune MRL-lpr mice as revealed by Fluoro Jade B staining. Brain Res 964(2):200–210

    Article  CAS  PubMed  Google Scholar 

  80. Del Bigio MR (1993) Neuropathological changes caused by hydrocephalus. Acta Neuropathol 85(6):573–585

    Article  PubMed  Google Scholar 

  81. Gerber J, Raivich G, Wellmer A, Noeske C, Kunst T, Werner A, Bruck W, Nau R (2001) A mouse model of Streptococcus pneumoniae meningitis mimicking several features of human disease. Acta Neuropathol 101(5):499–508

    CAS  PubMed  Google Scholar 

  82. Alexander EL, Alexander GE (1983) Aseptic meningoencephalitis in primary Sjogren's syndrome. Neurology 33:593–598

    Article  CAS  PubMed  Google Scholar 

  83. Auer RN, Wieloch T, Olsson Y, Siesjo BK (1984) The distribution of hypoglycemic brain damage. Acta Neuropathol 64(3):177–191

    Article  CAS  PubMed  Google Scholar 

  84. Fujioka M, Okuchi K, Hiramatsu KI, Sakaki T, Sakaguchi S, Ishii Y (1997) Specific changes in human brain after hypoglycemic injury. Stroke 28(3):584–587

    Article  CAS  PubMed  Google Scholar 

  85. Denenberg VH, Sherman GF, Rosen GD, Morrison L, Behan PO, Galaburda AM (1992) A behavior profile of the MRL/Mp lpr/lpr mouse and its association with hydrocephalus. Brain Behav Immun 6:40–49

    Article  CAS  PubMed  Google Scholar 

  86. Alexander JJ, Zwingmann C, Quigg R (2005) MRL/lpr mice have alterations in brain metabolism as shown with [(1)H-(13)C] NMR spectroscopy. Neurochem Int 47(1–2):143–151

    Article  CAS  PubMed  Google Scholar 

  87. Alexander JJ, Bao L, Jacob A, Kraus DM, Holers VM, Quigg RJ (2003) Administration of the soluble complement inhibitor, Crry-Ig, reduces inflammation and aquaporin 4 expression in lupus cerebritis. Biochim Biophys Acta 1639(3):169–176

    Article  CAS  PubMed  Google Scholar 

  88. Hampton DW, Seitz A, Chen P, Heber-Katz E, Fawcett JW (2004) Altered CNS response to injury in the MRL/MpJ mouse. Neuroscience 127(4):821–832

    Article  CAS  PubMed  Google Scholar 

  89. Lawson LJ, Perry VH, Dri P, Gordon S (1990) Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain. Neuroscience 39(1):151–170

    Article  CAS  PubMed  Google Scholar 

  90. Ballok DA, Earls AM, Krasnik C, Hoffman SA, Sakic B (2004) Autoimmune-induced damage of the midbrain dopaminergic system in lupus-prone mice. J Neuroimmunol 152(1–2):83–97

    Article  CAS  PubMed  Google Scholar 

  91. Hess DC (1997) Cerebral lupus vasculopathy. Mechanisms and clinical relevance. Ann N Y Acad Sci 823:154–168

    Article  CAS  PubMed  Google Scholar 

  92. Baraczka K, Nekam K, Pozsonyi T, Jakab L, Szongoth M, Sesztak M (2001) Concentration of soluble adhesion molecules (sVCAM-1, sICAM-1 and sL-selectin) in the cerebrospinal fluid and serum of patients with multiple sclerosis and systemic lupus erythematosus with central nervous involvement. Neuroimmunomodulation 9(1):49–54

    Article  CAS  PubMed  Google Scholar 

  93. Chinn RJS, Wilkinson ID, Hallcraggs MA, Paley MNJ, Shorthall E, Carter S, Kendall BE, Isenberg DA, Newman SP, Harrison MJG (1997) Magnetic resonance imaging of the brain and cerebral proton spectroscopy in patients with systemic lupus erythematosus. Arthritis Rheum 40(1):36–46

    Article  CAS  PubMed  Google Scholar 

  94. Rocca MA, Agosta F, Mezzapesa DM, Ciboddo G, Falini A, Comi G, Filippi M (2006) An fMRI study of the motor system in patients with neuropsychiatric systemic lupus erythematosus. Neuroimage 30(2):478–484

    Article  PubMed  Google Scholar 

  95. Sled JG, Spring S, van Eede M, Lerch JP, Ullal S, Sakic B (2009) Time course and nature of brain atrophy in the MRL mouse model of central nervous system lupus. Arthritis Rheum 60(6):1764–1774

    Article  PubMed  Google Scholar 

  96. Sakic B, Szechtman H, Denburg JA, Gorny G, Kolb B, Whishaw IQ (1998) Progressive atrophy of pyramidal neuron dendrites in autoimmune MRL-lpr mice. J Neuroimmunol 87(1–2):162–170

    Article  CAS  PubMed  Google Scholar 

  97. Maric D, Millward JM, Ballok DA, Szechtman H, Barker JL, Denburg JA, Sakic B (2001) Neurotoxic properties of cerebrospinal fluid from behaviorally impaired autoimmune mice. Brain Res 920(1–2):183–193

    Article  CAS  PubMed  Google Scholar 

  98. Kovac AD, Grammig J, Mahlo J, Steiner B, Roth K, Nitsch R, Bechmann I (2002) Comparison of neuronal density and subfield sizes in the hippocampus of CD95L-deficient (gld), CD95-deficient (lpr) and nondeficient mice. Eur J Neurosci 16(1):159–163

    Article  PubMed  Google Scholar 

  99. Sakic B, Maric I, Koeberle PD, Millward JM, Szechtman H, Maric D, Denburg JA (2000) Increased TUNEL-staining in brains of autoimmune Fas-deficient mice. J Neuroimmunol 104(2):147–154

    Article  CAS  PubMed  Google Scholar 

  100. Yamashita T, Ninomiya M, Hernandez AP, Garcia-Verdugo JM, Sunabori T, Sakaguchi M, Adachi K, Kojima T, Hirota Y, Kawase T, Araki N, Abe K, Okano H, Sawamoto K (2006) Subventricular zone-derived neuroblasts migrate and differentiate into mature neurons in the post-stroke adult striatum. J Neurosci 26(24):6627–6636

    Article  CAS  PubMed  Google Scholar 

  101. Sakic B, Kirkham DL, Ballok DA, Mwanjewe J, Fearon IM, Macri J, Yu G, Sidor MM, Denburg JA, Szechtman H, Lau J, Ball AK, Doering LC (2005) Proliferating brain cells are a target of neurotoxic CSF in systemic autoimmune disease. J Neuroimmunol 169(1–2):68–85

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Lechner O, Dietrich H, Oliveira dos SA, Wiegers GJ, Schwarz S, Harbutz M, Herold M, Wick G (2000) Altered circadian rhythms of the stress hormone and melatonin response in lupus-prone MRL/MP-fas(Ipr) mice. J Autoimmun 14(4):325–333

    Article  CAS  PubMed  Google Scholar 

  103. Mirescu C, Gould E (2006) Stress and adult neurogenesis. Hippocampus 16(3):233–238

    Article  CAS  PubMed  Google Scholar 

  104. Anderson KK, Ballok DA, Prasad N, Szechtman H, Sakic B (2006) Impaired response to amphetamine and neuronal degeneration in the nucleus accumbens of autoimmune MRL-lpr mice. Behav Brain Res 166:32–38

    Article  CAS  PubMed  Google Scholar 

  105. Brey RL, Cote S, Barohn R, Jackson C, Crawley R, Teale JM (1995) Model for the neuromuscular complications of systemic lupus erythematosus. Lupus 4(3):209–212

    Article  CAS  PubMed  Google Scholar 

  106. Loheswaran G, Stanojcic M, Xu L, Sakic B (2010) Autoimmunity as a principal pathogenic factor in the refined model of neuropsychiatric lupus. Clin Exp Neuroimmunol 1:141–152

    Article  CAS  Google Scholar 

  107. How A, Dent PB, Liao SK, Denburg JA (1985) Antineuronal antibodies in neuropsychiatric systemic lupus erythematosus. Arthritis Rheum 28:789–795

    Article  CAS  PubMed  Google Scholar 

  108. Williams GW, Bluestein HG, Steinberg AD (1981) Brain-reactive lymphocytotoxic antibody in the cerebrospinal fluid of patients with systemic lupus erythematosus: correlation with central nervous system involvement. Clin Immunol Immunopathol 18(1):126–132

    Article  CAS  PubMed  Google Scholar 

  109. Bluestein HG, Zvaifler NJ (1976) Brain-reactive lymphocytotoxic antibodies in the serum of patients with systemic lupus erythematosus. J Clin Invest 57(2):509–516

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Bresnihan B, Hohmeister R, Cutting J, Travers RL, Waldburger M, Black C, Jones T, Hughes GR (1979) The neuropsychiatric disorder in systemic lupus erythematosus: evidence for both vascular and immune mechanisms. Ann Rheum Dis 38(4):301–306

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Golombek SJ, Graus F, Elkon KB (1986) Autoantibodies in the cerebrospinal fluid of patients with systemic lupus erythematosus. Arthritis Rheum 29(9):1090–1097

    Article  CAS  PubMed  Google Scholar 

  112. Quismorio FP, Friou GJ (1972) Antibodies reactive with neurons in SLE patients with neuropsychiatric manifestations. Int Arch Allergy Appl Immunol 43:740–748

    Article  CAS  PubMed  Google Scholar 

  113. DeGiorgio LA, Konstantinov KN, Lee SC, Hardin JA, Volpe BT, Diamond B (2001) A subset of lupus anti-DNA antibodies cross-reacts with the NR2 glutamate receptor in systemic lupus erythematosus. Nat Med 7(11):1189–1193

    Article  CAS  PubMed  Google Scholar 

  114. Tanaka S, Matsunaga H, Kimura M, Tatsumi K, Hidaka Y, Takano T, Uema T, Takeda M, Amino N (2003) Autoantibodies against four kinds of neurotransmitter receptors in psychiatric disorders. J Neuroimmunol 141(1–2):155–164

    Article  CAS  PubMed  Google Scholar 

  115. Zandman-Goddard G, Chapman J, Shoenfeld Y (2007) Autoantibodies involved in neuropsychiatric SLE and antiphospholipid syndrome. Semin Arthritis Rheum 36(5):297–315

    Article  CAS  PubMed  Google Scholar 

  116. Isshi K, Hirohata S (1996) Association of anti-ribosomal P protein antibodies with neuropsychiatric systemic lupus erythematosus. Arthritis Rheum 39(9):1483–1490

    Article  CAS  PubMed  Google Scholar 

  117. Denburg SD, Denburg JA (2003) Cognitive dysfunction and antiphospholipid antibodies in systemic lupus erythematosus. Lupus 12(12):883–890

    Article  CAS  PubMed  Google Scholar 

  118. Hanly JG, Urowitz MB, Siannis F, Farewell V, Gordon C, Bae SC, Isenberg D, Dooley MA, Clarke A, Bernatsky S, Gladman D, Fortin PR, Manzi S, Steinsson K, Bruce IN, Ginzler E, Aranow C, Wallace DJ, Ramsey-Goldman R, van Vollenhoven R, Sturfelt G, Nived O, Sanchez-Guerrero J, Alarcon GS, Petri M, Khamashta M, Zoma A, Font J, Kalunian K, Douglas J, Qi Q, Thompson K, Merrill JT (2008) Autoantibodies and neuropsychiatric events at the time of systemic lupus erythematosus diagnosis: results from an international inception cohort study. Arthritis Rheum 58(3):843–853

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Kowal C, DeGiorgio LA, Nakaoka T, Hetherington H, Huerta PT, Diamond B, Volpe BT (2004) Cognition and immunity; antibody impairs memory. Immunity 21(2):179–188

    Article  CAS  PubMed  Google Scholar 

  120. Huerta PT, Kowal C, DeGiorgio LA, Volpe BT, Diamond B (2006) Immunity and behavior: antibodies alter emotion. Proc Natl Acad Sci U S A 103(3):678–683

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Kowal C, DeGiorgio LA, Lee JY, Edgar MA, Huerta PT, Volpe BT, Diamond B (2006) Human lupus autoantibodies against NMDA receptors mediate cognitive impairment. Proc Natl Acad Sci U S A 103(52):19854–19859

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Ndhlovu M, Preuss BE, Dengjel J, Stevanovic S, Weiner SM, Klein R (2011) Identification of alpha-tubulin as an autoantigen recognized by sera from patients with neuropsychiatric systemic lupus erythematosus. Brain Behav Immun 25(2):279–285

    Article  CAS  PubMed  Google Scholar 

  123. Colasanti T, Delunardo F, Margutti P, Vacirca D, Piro E, Siracusano A, Ortona E (2009) Autoantibodies involved in neuropsychiatric manifestations associated with systemic lupus erythematosus. J Neuroimmunol 212(1–2):3–9

    Article  CAS  PubMed  Google Scholar 

  124. Lefranc D, Launay D, Dubucquoi S, de SJ, Dussart P, Vermersch M, Hachulla E, Hatron PY, Vermersch P, Mouthon L, Prin L (2007) Characterization of discriminant human brain antigenic targets in neuropsychiatric systemic lupus erythematosus using an immunoproteomic approach. Arthritis Rheum 56(10):3420–3432

    Article  CAS  PubMed  Google Scholar 

  125. Williams RC Jr, Sugiura K, Tan EM (2004) Antibodies to microtubule-associated protein 2 in patients with neuropsychiatric systemic lupus erythematosus. Arthritis Rheum 50(4):1239–1247

    Article  CAS  PubMed  Google Scholar 

  126. Yoshio T, Onda K, Nara H, Minota S (2006) Association of IgG anti-NR2 glutamate receptor antibodies in cerebrospinal fluid with neuropsychiatric systemic lupus erythematosus. Arthritis Rheum 54(2):675–678

    Article  CAS  PubMed  Google Scholar 

  127. Arinuma Y, Yanagida T, Hirohata S (2008) Association of cerebrospinal fluid anti-NR2 glutamate receptor antibodies with diffuse neuropsychiatric systemic lupus erythematosus. Arthritis Rheum 58(4):1130–1135

    Article  CAS  PubMed  Google Scholar 

  128. Stanojcic M, Loheswaran G, Xu L, Hoffman SA, Sakic B (2010) Intrathecal antibodies and brain damage in autoimmune MRL mice. Brain Behav Immun 24:289–297

    Article  CAS  PubMed  Google Scholar 

  129. Hoffman SA, Madsen CS (1990) Brain specific autoantibodies in murine models of systemic lupus erythematosus. J Neuroimmunol 30:229–237

    Article  CAS  PubMed  Google Scholar 

  130. Hoffman SA, Arbogast DN, Ford PM, Shucard DW, Harbeck RJ (1987) Brain-reactive autoantibody levels in the sera of ageing autoimmune mice. Clin Exp Immunol 70:74–83

    CAS  PubMed  PubMed Central  Google Scholar 

  131. Crimando J, Hoffman SA (1992) Detection of brain-reactive autoantibodies in the sera of autoimmune mice using ELISA. J Immunol Methods 149:87–95

    Article  CAS  PubMed  Google Scholar 

  132. Sakic B, Szechtman H, Denburg SD, Carbotte RM, Denburg JA (1993) Brain-reactive antibodies and behavior of autoimmune MRL-lpr mice. Physiol Behav 54:1025–1029

    Article  CAS  PubMed  Google Scholar 

  133. Gao HX, Sanders E, Tieng AT, Putterman C (2010) Sex and autoantibody titers determine the development of neuropsychiatric manifestations in lupus-prone mice. J Neuroimmunol 229(1–2):112–122

    Article  CAS  PubMed  Google Scholar 

  134. Gao HX, Campbell SR, Cui MH, Zong P, Hee-Hwang J, Gulinello M, Putterman C (2009) Depression is an early disease manifestation in lupus-prone MRL/lpr mice. J Neuroimmunol 207(1–2):45–56

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Hoffman SA, Sakic B (2008) Autoimmunity and brain dysfunction. In: Siegel A, Zalcman S (eds) The neuroimmunological basis of behavior and mental disorders. Springer-Verlag, Boston, MA

    Google Scholar 

  136. Meroni PL, Tincani A, Sepp N, Raschi E, Testoni C, Corsini E, Cavazzana I, Pellegrini S, Salmaggi A (2003) Endothelium and the brain in CNS lupus. Lupus 12(12):919–928

    Article  CAS  PubMed  Google Scholar 

  137. Tang B, Matsuda T, Akira S, Nagata N, Ikehara S, Hirano T, Kishimoto T (1991) Age-associated increase in interleukin 6 in MRL/lpr mice. Int Immunol 3:273–278

    Article  CAS  PubMed  Google Scholar 

  138. Singh AK, Lebedeva TV (1994) Interleukin-1 contributes to high level IgG production in the murine MRL/lpr lupus model. Immunol Invest 23:281–292

    Article  CAS  PubMed  Google Scholar 

  139. Boswell JM, Yui MA, Endres S, Burt DW, Kelley VE (1988) Novel and enhanced IL-1 gene expression in autoimmune mice with lupus. J Immunol 141:118–124

    CAS  PubMed  Google Scholar 

  140. Sakic B, Szechtman H, Braciak TA, Richards CD, Gauldie J, Denburg JA (1997) Reduced preference for sucrose in autoimmune mice: a possible role of interleukin-6. Brain Res Bull 44(2):155–165

    Article  CAS  PubMed  Google Scholar 

  141. Kwant A, Sakic B (2004) Behavioral effects of infection with interferon-gamma adenovector. Behav Brain Res 151(1–2):73–82

    Article  CAS  PubMed  Google Scholar 

  142. Sakic B, Szechtman H, Gauldie J, Denburg JA (2001) Behavioral effects of infection with IL-6 adenovector. Brain Behav Immun 15(1):25–42

    Article  CAS  PubMed  Google Scholar 

  143. Marshall D, Dangerfield JP, Bhatia VK, Larbi KY, Nourshargh S, Haskard DO (2003) MRL/lpr lupus-prone mice show exaggerated ICAM-1-dependent leucocyte adhesion and transendothelial migration in response to TNF-alpha. Rheumatology (Oxford) 42(8):929–934

    Article  CAS  Google Scholar 

  144. Banks WA, Kastin AJ, Gutierrez EG (1994) Penetration of interleukin-6 across the murine blood-brain barrier. Neurosci Lett 179(1–2):53–56

    Article  CAS  PubMed  Google Scholar 

  145. Banks WA, Kastin AJ, Gutierrez EG (1993) Interleukin-1 alpha in blood has direct access to cortical brain cells. Neurosci Lett 163(1):41–44

    Article  CAS  PubMed  Google Scholar 

  146. Gutierrez EG, Banks WA, Kastin AJ (1993) Murine tumor necrosis factor alpha is transported from blood to brain in the mouse. J Neuroimmunol 47(2):169–176

    Article  CAS  PubMed  Google Scholar 

  147. Tsai CY, Wu TH, Tsai ST, Chen KH, Thajeb P, Lin WM, Yu HS, Yu CL (1994) Cerebrospinal fluid interleukin-6, prostaglandin E2 and autoantibodies in patients with neuropsychiatric systemic lupus erythematosus and central nervous system infections. Scand J Rheumatol 23(2):57–63

    Article  CAS  PubMed  Google Scholar 

  148. Svenungsson E, Andersson M, Brundin L, van Vollenhoven R, Khademi M, Tarkowski A, Greitz D, Dahlstrom M, Lundberg I, Klareskog L, Olsson T (2001) Increased levels of proinflammatory cytokines and nitric oxide metabolites in neuropsychiatric lupus erythematosus. Ann Rheum Dis 60(4):372–379

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Hayley S, Merali Z, Anisman H (2003) Stress and cytokine-elicited neuroendocrine and neurotransmitter sensitization: implications for depressive illness. Stress 6(1):19–32

    Article  CAS  PubMed  Google Scholar 

  150. Hu Y, Dietrich H, Herold M, Heinrich PC, Wick G (1993) Disturbed immuno-endocrine communication via the hypothalamo- pituitary-adrenal axis in autoimmune disease. Int Arch Allergy Immunol 102:232–241

    Article  CAS  PubMed  Google Scholar 

  151. Rivier C, Rivest S (1993) Mechanisms mediating the effects of cytokines on neuroendocrine functions in the rat. In: Chadwick D, Marsh J, Ackrill K (eds) Corticotropin-releasing factor, vol Clayton Foundation Laboratories for Peptide Biology, Salk Institute, San Diego, CA 92128, Ciba Foundation Symposium, vol 172. John Wiley & Sons, Chichester, pp 204–225

    Google Scholar 

  152. Spangelo BL, Gorospe WC (1995) Role of the cytokines in the neuroendocrine-immune system axis. Front Neuroendocrinol 16(1):1–22

    Article  CAS  PubMed  Google Scholar 

  153. Miller AH, Maletic V, Raison CL (2009) Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry 65(9):732–741

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Del Rey A, Besedovsky HO (2000) The cytokine-HPA axis circuit contributes to prevent or moderate autoimmune processes. Z Rheumatol 59(Suppl 2):II/31–II/35

    Google Scholar 

  155. Lorton D, Lubahn C, Bellinger DL (2003) Potential use of drugs that target neural-immune pathways in the treatment of rheumatoid arthritis and other autoimmune diseases. Curr Drug Targets Inflamm Allergy 2(1):1–30

    Article  CAS  PubMed  Google Scholar 

  156. Spangelo BL, Judd AM, Call GB, Zumwalt J, Gorospe WC (1995) Role of the cytokines in the hypothalamic-pituitary-adrenal and gonadal axes. Neuroimmunomodulation 2(5):299–312

    Article  CAS  PubMed  Google Scholar 

  157. Spangelo BL, Judd AM, Isakson PC, MacLeod RM (1989) Interleukin-6 stimulates anterior pituitary hormone release in vitro. Endocrinology 125(1):575–577

    Article  CAS  PubMed  Google Scholar 

  158. Shanks N, Moore PM, Perks P, Lightman SL (1999) Alterations in hypothalamic-pituitary-adrenal function correlated with the onset of murine SLE in MRL +/+ and lpr/lpr mice. Brain Behav Immun 13(4):348–360

    Article  CAS  PubMed  Google Scholar 

  159. Sakic B, Laflamme N, Crnic LS, Szechtman H, Denburg JA, Rivest S (1999) Reduced corticotropin-releasing factor and enhanced vasopressin gene expression in brains of mice with autoimmunity-induced behavioral dysfunction. J Neuroimmunol 96(1):80–91

    Article  CAS  PubMed  Google Scholar 

  160. McEwen BS (1999) Stress and the aging hippocampus. Front Neuroendocrinol 20(1):49–70

    Article  CAS  PubMed  Google Scholar 

  161. Woolley CS, Gould E, McEwen BS (1990) Exposure to excess glucocorticoids alters dendritic morphology of adult hippocampal pyramidal neurons. Brain Res 531(1–2):225–231

    Article  CAS  PubMed  Google Scholar 

  162. Ballok DA, Sakic B (2008) Purine receptor antagonist modulates serology and affective behaviors in lupus-prone mice: evidence of autoimmune-induced pain? Brain Behav Immun 22(8):1208–1216

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Sapolsky RM (2000) Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders. Arch Gen Psychiatry 57(10):925–935

    Article  CAS  PubMed  Google Scholar 

  164. Peress NS, Roxburgh VA, Gelfand MC (1981) Binding sites for immune components in human choroid plexus. Arthritis Rheum 24(3):520–526

    Article  CAS  PubMed  Google Scholar 

  165. Schwartz MM, Roberts JL (1983) Membranous and vascular choroidopathy: two patterns of immune deposits in systemic lupus erythematosus. Clin Immunol Immunopathol 29(3):369–380

    Article  CAS  PubMed  Google Scholar 

  166. Reilly CM, Oates JC, Cook JA, Morrow JD, Halushka PV, Gilkeson GS (2000) Inhibition of mesangial cell nitric oxide in MRL/lpr mice by prostaglandin J2 and proliferator activation receptor-gamma agonists. J Immunol 164(3):1498–1504

    Article  CAS  PubMed  Google Scholar 

  167. O’Sullivan FX, Vogelweid CM, Beschwilliford CL, Walker SE (1995) Differential effects of CD4(+) T cell depletion on inflammatory central nervous system disease, arthritis and sialadenitis in MRL/lpr mice. J Autoimmun 8:163–175

    Article  PubMed  Google Scholar 

  168. Jacob A, Hack B, Bai T, Brorson JR, Quigg RJ, Alexander JJ (2010) Inhibition of C5a receptor alleviates experimental CNS lupus. J Neuroimmunol 221(1–2):46–52

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Sakic B, Lacosta S, Denburg J, Szechtman H (2002) Altered neurotransmission in brains of autoimmune mice: pharmacological and neurochemical evidence. J Neuroimmunol 129(1–2):84–96

    Article  CAS  PubMed  Google Scholar 

  170. Chun S, McEvilly R, Foster JA, Sakic B (2008) Proclivity to self-injurious behavior in MRL-lpr mice: implications for autoimmunity-induced damage in the dopaminergic system. Mol Psychiatry 13(11):1043–1053

    Article  CAS  PubMed  Google Scholar 

  171. Wen J, Doerner J, Chalmers S, Stock A, Wang H, Gullinello M, Shlomchik MJ, Putterman C (2016) B cell and/or autoantibody deficiency do not prevent neuropsychiatric disease in murine systemic lupus erythematosus. J Neuroinflammation 13(1):73. https://doi.org/10.1186/s12974-016-0537-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Loheswaran G, Kapadia M, Gladman M, Pulapaka S, Xu L, Stanojcic M, Sakic B (2013) Altered neuroendocrine status at the onset of CNS lupus-like disease. Brain Behav Immun 32:86–93

    Article  CAS  PubMed  Google Scholar 

  173. Stock AD, Wen J, Doerner J, Herlitz LC, Gulinello M, Putterman C (2015) Neuropsychiatric systemic lupus erythematosus persists despite attenuation of systemic disease in MRL/lpr mice. J Neuroinflammation 12:205. https://doi.org/10.1186/s12974-015-0423-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Denenberg VH, Mobraaten LE, Sherman GF, Morrison L, Schrott LM, Waters NS, Rosen GD, Behan PO, Galaburda AM (1991) Effects of the autoimmune uterine/maternal environment upon cortical ectopias, behavior and autoimmunity. Brain Res 563:114–122

    Article  CAS  PubMed  Google Scholar 

  175. Lee JY, Huerta PT, Zhang J, Kowal C, Bertini E, Volpe BT, Diamond B (2009) Neurotoxic autoantibodies mediate congenital cortical impairment of offspring in maternal lupus. Nat Med 15(1):91–96

    Article  CAS  PubMed  Google Scholar 

  176. Li Y, Eskelund AR, Zhou H, Budac DP, Sanchez C, Gulinello M (2015) Behavioral deficits are accompanied by immunological and neurochemical changes in a mouse model for neuropsychiatric lupus (NP-SLE). Int J Mol Sci 16(7):15150–15171. https://doi.org/10.3390/ijms160715150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Wen J, Doerner J, Weidenheim K, Xia Y, Stock A, Michaelson JS, Baruch K, Deczkowska A, Gulinello M, Schwartz M, Burkly LC, Putterman C (2015) TNF-like weak inducer of apoptosis promotes blood brain barrier disruption and increases neuronal cell death in MRL/lpr mice. J Autoimmun 60:40–50. https://doi.org/10.1016/j.jaut.2015.03.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Wen J, Chen CH, Stock A, Doerner J, Gulinello M, Putterman C (2016) Intracerebroventricular administration of TNF-like weak inducer of apoptosis induces depression-like behavior and cognitive dysfunction in non-autoimmune mice. Brain Behav Immun 54:27–37. https://doi.org/10.1016/j.bbi.2015.12.017

    Article  CAS  PubMed  Google Scholar 

  179. Marcinko K, Parsons T, Lerch JP, Sled JG, Sakic B (2013) Effects of prolonged treatment with memantine in the MRL model of CNS lupus. Clin Exp Neuroimmunol 3(3):116–128

    Article  CAS  Google Scholar 

  180. Kapadia M, Zhao H, Ma D, Sakic B (2017) Sustained immunosuppression alters olfactory function in the MRL model of CNS lupus. J Neuroimmune Pharmacol 12(3):555–564. https://doi.org/10.1007/s11481-017-9745-6

    Article  PubMed  Google Scholar 

  181. Mahajan SD, Tutino VM, Redae Y, Meng H, Siddiqui A, Woodruff TM, Jarvis JN, Hennon T, Schwartz S, Quigg RJ, Alexander JJ (2016) C5a induces caspase-dependent apoptosis in brain vascular endothelial cells in experimental lupus. Immunology 148(4):407–419. https://doi.org/10.1111/imm.12619

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. Chalmers SA, Wen J, Shum J, Doerner J, Herlitz L, Putterman C (2017) CSF-1R inhibition attenuates renal and neuropsychiatric disease in murine lupus. Clin Immun (Orlando, Fla) 185:100–108. https://doi.org/10.1016/j.clim.2016.08.019

    Article  CAS  Google Scholar 

  183. Kim A, Feng P, Ohkuri T, Sauers D, Cohn ZJ, Chai J, Nelson T, Bachmanov AA, Huang L, Wang H (2012) Defects in the peripheral taste structure and function in the MRL/lpr mouse model of autoimmune disease. PLoS One 7(4):e35588

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. Kapadia M, Stanojcic M, Earls AM, Pulapaka S, Lee J, Sakic B (2012) Altered olfactory function in the MRL model of CNS lupus. Behav Brain Res 234(2):303–311

    Article  PubMed  Google Scholar 

  185. Stanojcic M, Burstyn-Cohen T, Nashi N, Lemke G, Sakic B (2009) Disturbed distribution of proliferative brain cells during lupus-like disease. Brain Behav Immun 23(7):1003–1013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This work was supported by the grants from the Ontario Mental Health Foundation and Canadian Institutes of Heath Research.

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  1. Department of Psychiatry and Behavioral Neurosciences, McMaster University, Hamilton, ON, Canada

    Boris Šakić

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  1. University of Maryland University College, Adelphi, MD, PharmTao, Santa Clara, California, USA

    Qing Yan

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Šakić, B. (2018). The MRL Model: A Valuable Tool in Studies of Autoimmunity-Brain Interactions. In: Yan, Q. (eds) Psychoneuroimmunology. Methods in Molecular Biology, vol 1781. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7828-1_14

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