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Alternative Complement Pathway in Schizophrenia

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Abstract

In the present study, we evaluated functional activity of the alternative pathway of complement in schizophrenia by measuring the alternative pathway hemolytic activity (AH50) of complement as well as hemolytic activity of the complement C3 component (C3H50) in the blood of patients with schizophrenia and healthy subjects. To assess the influence of neuroleptic treatment on measured parameters, both drug-free and medicated patients were examined. In addition, correlation analysis between AH50 and C3H50 has been performed. The results of the present study clearly demonstrate upregulation of the alternative complement cascade in schizophrenia and activator effect of neuroleptics on complement alternative pathway. Based upon the results obtained we hypothesize that hyperactivation of the alternative complement pathway in schizophrenia is stimulated by apoptotic cells.

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References

  1. Sim RB, Laich A (2000) Serine proteases of the complement system. Biochem Soc Trans 28(5):545–550

    CAS  PubMed  Google Scholar 

  2. Cole DS, Morgan BP (2003) Beyond lysis: how complement influences cell fate. Clin Sci 104:455–466

    Article  CAS  PubMed  Google Scholar 

  3. Nauta AJ, Roos A, Daha MR (2004) A regulatory role for complement in innate immunity and autoimmunity. Int Arch Allergy Immunol 134(4):310–323

    Article  CAS  PubMed  Google Scholar 

  4. Paccaud JP, Carpentier JL, Schifferli JA (1990) Difference in the clustering of complement receptor type 1 (CR1) on polymorphonuclear leukocytes and erythrocytes: effect on immune adherence. Eur J Immunol 20(2):283–289

    Article  CAS  PubMed  Google Scholar 

  5. Wetsel RA (1995) Structure, function and cellular expression of complement anaphylatoxin receptors. Curr Opin Immunol 7(1):48–53

    Article  CAS  PubMed  Google Scholar 

  6. Fureder W, Agis H, Willheim M et al (1995) Differential expression of complement receptors on human basophils and mast cells. Evidence for mast cell heterogeneity and CD88/C5aR expression on skin mast cells. J Immunol 155(6):3152–3160

    CAS  PubMed  Google Scholar 

  7. Tenner AJ (1999) Membrane receptors for soluble defense collagens. Curr Opin Immunol 11(1):34–41

    Article  CAS  PubMed  Google Scholar 

  8. Cherukuri A, Cheng PC, Pierce SK (2001) The role of the CD19/CD21 complex in B cell processing and presentation of complement-tagged antigens. J Immunol 167(1):163–172

    CAS  PubMed  Google Scholar 

  9. Drouin SM, Kildsgaard J, Haviland J et al (2001) Expression of the complement anaphylatoxin C3a and C5a receptors on bronchial epithelial and smooth muscle cells in models of sepsis and asthma. J Immunol 166(3):2025–2032

    CAS  PubMed  Google Scholar 

  10. Godau J, Heller T, Hawlisch H et al (2004) C5a initiates the inflammatory cascade in immune complex peritonitis. J Immunol 173(5):3437–3445

    CAS  PubMed  Google Scholar 

  11. Zaidi AK, Amrani Y, Panettieri RA, Ali H (2006) Response to C3a, mast cells, and asthma. FASEB J 20(2):199

    Article  CAS  PubMed  Google Scholar 

  12. Wakabayashi M, Ohi H, Tamano M et al (2006) Acquired loss of erythrocyte complement receptor type 1 in patients with diabetic nephropathy undergoing hemodialysis. Nephron Exp Nephrol 104(3):e89–e95

    Article  CAS  PubMed  Google Scholar 

  13. Rahpeymai Y, Hietala MA, Wilhelmsson U et al (2006) Complement: a novel factor in basal and ischemia-induced neurogenesis. EMBO J 25:1364–1374

    Article  CAS  PubMed  Google Scholar 

  14. Fourgeaud L, Boulanger LM (2007) Synapse remodeling, compliments of the complement system. Cell 131(6):1034–1036

    Article  CAS  PubMed  Google Scholar 

  15. Stevens B, Allen NJ, Vazquez LE et al (2007) The classical complement cascade mediates CNS synapse elimination. Cell 131(6):1164–1178

    Article  CAS  PubMed  Google Scholar 

  16. Woods BT (1998) Is schizophrenia a progressive neurodevelopmental disorder? Toward a unitary pathogenetic mechanism. Am J Psychiatry 155:1661–1670

    CAS  PubMed  Google Scholar 

  17. Ashe PC, Berry MD, Boulton AA (2001) Schizophrenia, a neurodegenerative disorder with neurodevelopmental antecedents. Prog Neuropsychopharmacol Biol Psychiatry 25:691–707

    Article  CAS  PubMed  Google Scholar 

  18. Lewis DA, Levitt P (2002) Schizophrenia as a disorder of neurodevelopment. Ann Rev Neurosci 25:409–432

    Article  CAS  PubMed  Google Scholar 

  19. Jaaro-Peled H, Hayashi-Takagi A, Seshadri S et al (2009) Neurodevelopmental mechanisms of schizophrenia: understanding disturbed postnatal brain maturation through neuregulin-1—ErbB4 and DISC1. Trends Neurosci 32(9):485–495

    Article  CAS  PubMed  Google Scholar 

  20. Margolis RL, Chuang DM, Post RM (1994) Programmed cell death: implications for neuropsychiatric disorders. Biol Psychiatry 35:946–956

    Article  CAS  PubMed  Google Scholar 

  21. Knable MB (1999) Schizophrenia and bipolar disorder: findings from studies of the Stanley foundation brain collection. Schizophr Res 39:149–152

    Article  CAS  PubMed  Google Scholar 

  22. Lewis DA, Lieberman JA (2000) Catching up on schizophrenia: natural history and neurobiology. Neuron 28:325–334

    Article  CAS  PubMed  Google Scholar 

  23. Jarskog LF, Gilmore JH, Selinger ES, Lieberman JA (2000) Cortical bcl-2 protein expression and apoptotic regulation in schizophrenia. Biol Psychiatry 48:641–650

    Article  CAS  PubMed  Google Scholar 

  24. Catts VS, Catts SV (2000) Apoptosis and schizophrenia: is the tumour suppressor gene, p53, a candidate susceptibility gene? Schizoph Res 41:405–415

    Article  CAS  Google Scholar 

  25. Benes FM (2000) Emerging principles of altered neural circuitry in schizophrenia. Brain Res Rev 31:251–269

    Article  CAS  PubMed  Google Scholar 

  26. Kozlovsky N, Belmaker RH, Agam G (2002) GSK-3 and the neurodevelopmental hypothesis of schizophrenia. Eur Neuropsychopharmacol 12(1):13–25

    Article  CAS  PubMed  Google Scholar 

  27. Berger GE, Wood S, McGorry PD (2003) Incipient neurovulnerability and neuroprotection in early psychosis. Psychopharmacol Bull 37:79–101

    PubMed  Google Scholar 

  28. Benes FM, Walsh J, Bhattacharyya S et al (2000) DNA fragmentation decreased in schizophrenia but not bipolar disorder. Arch Gen Psychiatry 60:359–364

    Article  Google Scholar 

  29. Benes FM (2004) The role of apoptosis in neuronal pathology in schizophrenia and bipolar disorder. Curr Opin Psychiatry 17(3):189–190

    Article  Google Scholar 

  30. Jarskog LF, Selinger ES, Lieberman JA et al (2004) Apoptotic proteins in the temporal cortex in schizophrenia: high Bax/Bcl-2 ratio without caspase-3 activation. Am J Psychiatry 161(1):109–115

    Article  PubMed  Google Scholar 

  31. Jarskog LF, Glantz LA, Gilmore JH et al (2005) Apoptotic mechanisms in the pathophysiology of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 29:846–858

    Article  CAS  PubMed  Google Scholar 

  32. Catts VS, Cans SV, McGrath JJ, Feron F, McLead D, Coulson EJ, Lutze-Mann LH (2006) Apoptosis and schizophrenia: a pilot study based on dermal fibroblast cell lines. Schizophr Res 84(1):20–28

    Article  PubMed  Google Scholar 

  33. Chen X, Wang X, Chen Q, Williamson V, van den OE et al (2008) MEGF10 association with schizophrenia. Biol Psychiatry 63:441–448

    Article  CAS  PubMed  Google Scholar 

  34. Chen X, Sun C, Chen Q, O’Neill FA, Walsh D et al (2009) Apoptotic engulfment pathway and schizophrenia. PLoS One 4(9):e6875. doi:10.1371/journal.pone.0006875

    Article  PubMed  Google Scholar 

  35. Hakobyan S, Boyajyan A, Sim RB (2005) Classical pathway complement activity in schizophrenia. Neurosci Lett 374(1):35–37

    Article  CAS  PubMed  Google Scholar 

  36. Verbovetski I, Bychkov H, Trahtemberg U et al (2002) Opsonization of apoptotic cells by autologous iC3b facilitates clearance by immature dendritic cells, down-regulates DR and CD86, and upregulates CC chemokine receptor 7. J Exp Med 196:1553–1561

    Article  CAS  PubMed  Google Scholar 

  37. Tsuji S, Kaji K, Nagasawa S (1994) Activation of the alternative pathway of human complement by apoptotic human umbilical vein endothelial cells. J Biochem (Tokyo) 116:794–800

    CAS  Google Scholar 

  38. Takizawa F, Tsuji S, Nagasawa S (1996) Enhancement of macrophage phagocytosis upon iC3b deposition on apoptotic cells. FEBS Lett 397:269–272

    Article  CAS  PubMed  Google Scholar 

  39. Galili-Mosberg R, Gil-Ad I, Weizman A et al (2000) Haloperidol induced neurotoxicity—possible implications for tardive dyskenezia. J Neural Transm 107(4):479–490

    Article  CAS  Google Scholar 

  40. Sachdev PS (2000) The current status of tardive dyskinesia. Aust N Z J Psychiatry 34(3):355–369

    CAS  PubMed  Google Scholar 

  41. Gil-ad I, Shtaif B, Shiloh R et al (2001) Evaluation of the neurotoxic activity of typical and atypical neuroleptics: relevance to iatrogenic extrapyramidal symptoms. Cell Mol Neurobiol 21(6):705–716

    Article  CAS  PubMed  Google Scholar 

  42. Marandi SN, Trimble N, Lee S (2004) The effects of neuroleptic drugs on apoptosis inducing factor protein. Biopharm J 8(4) (online)

  43. Whaley K, North J (1997) Haemolytic assays for whole complement activity and individual components. In: Doods AW, Sim RB (eds) Complement. A practical approach. Oxford University Press, Oxford, pp 19–47

    Google Scholar 

  44. Daha MR (1997) Purification of complement component. In: Doods AW, Sim RB (eds) Complement. A practical approach. Oxford University Press, Oxford, pp 121–133

    Google Scholar 

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Acknowledgments

We thank the medical staff of Nubarashen Psychiatric Hospital for their kind support to this study as well as our colleagues from the research institutes of the Armenian National Academy of Sciences and the Yerevan State University involved in our study as healthy subjects and kindly provided us with their blood samples.

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Correspondence to Anna Boyajyan.

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Special issue article in honor of Professor Armen Galoyan.

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Boyajyan, A., Khoyetsyan, A. & Chavushyan, A. Alternative Complement Pathway in Schizophrenia. Neurochem Res 35, 894–898 (2010). https://doi.org/10.1007/s11064-010-0126-2

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