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Proteome analyses of cultured astrocytes treated with MK-801 and clozapine: similarities with schizophrenia

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Abstract

On the basis of impaired glutamatergic transmission and the potential role of astrocytes in schizophrenia, we treated cultured astrocytes with MK-801, an NMDA-receptor antagonist, to investigate whether the resulting proteome changes are similar to those we found in our earlier proteome analysis of schizophrenia human brain tissue as well as to better comprehend the role of astrocytes in the disorder. Indeed, there are similarities. Furthermore, to verify the efficacy of clozapine and its effect over the proteome, we treated MK-801-treated astrocytes with clozapine. Interestingly, clozapine reversed protein changes induced by MK-801. The treatment of cell cultures with neural transmission agonists and antagonists might provide useful insights about psychiatric disorders.

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References

  1. Beasley CL, Pennington K, Behan A, Wait R, Dunn MJ, Cotter D (2006) Proteomic analysis of the anterior cingulate cortex in the major psychiatric disorders: evidence for disease-associated changes. Proteomics 6:3414–3425

    Article  PubMed  CAS  Google Scholar 

  2. Beasley CL, Honavar M, Everall IP, Cotter D (2009) Two-dimensional assessment of cytoarchitecture in the superior temporal white matter in schizophrenia, major depressive disorder and bipolar disorder. Schizophr Res 115(2–3):156–162

    Article  PubMed  Google Scholar 

  3. Behrens S, Gattaz WF (1992) MK-801 induced stereotypies in rats are decreased by haloperidol and increased by diazepam. J Neural Transm Gen Sect 90(3):219–224

    Article  PubMed  CAS  Google Scholar 

  4. Bernstein HG, Steiner J, Bogerts B (2009) Glial cells in schizophrenia: pathophysiological significance and possible consequences for therapy. Expert Rev Neurother 9(7):1059–1071

    Article  PubMed  CAS  Google Scholar 

  5. Chen JW, Dodia C, Feinstein SI, Jain MK, Fisher AB (2000) 1-Cys peroxiredoxin, a bifunctional enzyme with glutathione peroxidase and phospholipase A2 activities. J Biol Chem 275(37):28421–28427

    Article  PubMed  CAS  Google Scholar 

  6. Coan EJ, Saywood W, Collingridge GL (1987) MK-801 blocks NMDA receptor-mediated synaptic transmission and long term potentiation in rat hippocampal slices. Neurosci Lett 80(1):111–114

    Article  PubMed  CAS  Google Scholar 

  7. English JA, Dicker P, Föcking M, Dunn MJ, Cotter DR (2009) 2-D DIGE analysis implicates cytoskeletal abnormalities in psychiatric disease. Proteomics 9(12):3368–3382

    Article  PubMed  CAS  Google Scholar 

  8. Eyjolfsson EM, Brenner E, Kondziella D, Sonnewald U (2006) Repeated injection of MK801: an animal model of schizophrenia? Neurochem Int 48(6–7):541–546

    PubMed  CAS  Google Scholar 

  9. Fiacco TA, Agulhon C, McCarthy KD (2009) Sorting out astrocyte physiology from pharmacology. Annu Rev Pharmacol Toxicol 49:151–174

    Article  PubMed  CAS  Google Scholar 

  10. Hoffman DC (1992) Typical and atypical neuroleptics antagonize MK-801-induced locomotion and stereotypy in rats. J Neural Transm Gen Sect 89(1–2):1–10

    Article  PubMed  CAS  Google Scholar 

  11. Kondziella D, Brenner E, Eyjolfsson EM, Markinhuhta KR, Carlsson ML, Sonnewald U (2006) Glial-neuronal interactions are impaired in the schizophrenia model of repeated MK801 exposure. Neuropsychopharmacology 31(9):1880–1887

    Article  PubMed  CAS  Google Scholar 

  12. Martins-de-Souza D, Menezes de Oliveira B, dos Santos Farias A, Horiuchi RS, Crepaldi Domingues C, de Paula E, Marangoni S, Gattaz WF, Dias-Neto E, Camillo Novello J (2007) The use of ASB-14 in combination with CHAPS is the best for solubilization of human brain proteins for two-dimensional gel electrophoresis. Brief Funct Genomic Proteomic 6(1):70–75

    Article  PubMed  CAS  Google Scholar 

  13. Martins-de-Souza D, Gattaz WF, Schmitt A, Maccarrone G, Hunyadi-Gulyás E, Eberlin MN, Souza GH, Marangoni S, Novello JC, Turck CW, Dias-Neto E (2009) Proteomic analysis of dorsolateral prefrontal cortex indicates the involvement of cytoskeleton, oligodendrocyte, energy metabolism and new potential markers in schizophrenia. J Psychiatr Res 43(11):978–986

    Article  PubMed  Google Scholar 

  14. Martins-de-Souza D, Gattaz WF, Schmitt A, Rewerts C, Maccarrone G, Dias-Neto E, Turck CW (2009) Prefrontal cortex shotgun proteome analysis reveals altered calcium homeostasis and immune system imbalance in schizophrenia. Eur Arch Psychiatry Clin Neurosci 259(3):151–163

    Article  PubMed  Google Scholar 

  15. Martins-de-Souza D, Gattaz WF, Schmitt A, Rewerts C, Marangoni S, Novello JC, Maccarrone G, Turck CW, Dias-Neto E (2009) Alterations in oligodendrocyte proteins, calcium homeostasis and new potential markers in schizophrenia anterior temporal lobe are revealed by shotgun proteome analysis. J Neural Transm 116(3):275–289

    Article  PubMed  CAS  Google Scholar 

  16. Martins-de-Souza D, Gattaz WF, Schmitt A, Novello JC, Marangoni S, Turck CW, Dias-Neto E (2009) Proteome analysis of schizophrenia patients Wernicke’s area reveals an energy metabolism dysregulation. BMC Psychiatry 9:17

    Article  PubMed  Google Scholar 

  17. Martins-de-Souza D, Schmitt A, Röder R, Lebar M, Schneider-Axmann T, Falkai P, Turck CW (2010a) Sex-specific proteome differences in the anterior cingulate cortex of schizophrenia. J Psychiatr Res 44(14):989–991

    Article  PubMed  Google Scholar 

  18. Martins-de-Souza D, Maccarrone G, Wobrock T et al (2010b) Proteome analysis of the thalamus and cerebrospinal fluid reveals glycolysis dysfunction and potential biomarkers for schizophrenia. J Psychiatr Res. doi:10.1016/j.jpsychires.2010.04.014

  19. Martins-De-Souza D, Dias-Neto E, Schmitt A, Falkai P, Gormanns P, Maccarrone G, Turck CW, Gattaz WF (2010) Proteome analysis of schizophrenia brain tissue. World J Biol Psychiatry 11(2):110–120

    Article  PubMed  Google Scholar 

  20. Paulson L, Martin P, Ljung E, Blennow K, Davidsson P (2007) Proteome analysis after co-administration of clozapine or haloperidol to MK-801-treated rats. J Neural Transm 114(7):885–891

    Article  PubMed  CAS  Google Scholar 

  21. Paulson L, Martin P, Nilsson CL, Ljung E, Westman-Brinkmalm A, Blennow K, Davidsson P (2004) Comparative proteome analysis of thalamus in MK-801-treated rats. Proteomics 4(3):819–825

    Article  PubMed  CAS  Google Scholar 

  22. Paulson L, Martin P, Persson A, Nilsson CL, Ljung E, Westman-Brinkmalm A, Eriksson PS, Blennow K, Davidsson P (2003) Comparative genome- and proteome analysis of cerebral cortex from MK-801-treated rats. J Neurosci Res 71(4):526–533

    Article  PubMed  CAS  Google Scholar 

  23. Paz RD, Tardito S, Atzori M, Tseng KY (2008) Glutamatergic dysfunction in schizophrenia: from basic neuroscience to clinical psychopharmacology. Eur Neuropsychopharmacol 18(11):773–786

    Article  PubMed  CAS  Google Scholar 

  24. Prabakaran S, Swatton JE, Ryan MM, Huffaker SJ, Huang JT, Griffi n JL et al (2004) Mitochondrial dysfunction in schizophrenia: evidence for compromised brain metabolism and oxidative stress. Mol Psychiatry 9:684–697, 643

    Google Scholar 

  25. Rung JP, Carlsson A, Rydén Markinhuhta K, Carlsson ML (2005) (+)-MK-801 induced social withdrawal in rats; a model for negative symptoms of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 29(5):827–832

    Article  PubMed  CAS  Google Scholar 

  26. Russo-Marie F (1999) Annexin V and phospholipid metabolism. Clin Chem Lab Med 37(3):287–291

    Article  PubMed  CAS  Google Scholar 

  27. Schmitt A, Koschel J, Zink M, Bauer M, Sommer C, Frank J, Treutlein J, Schulze T, Schneider-Axmann T, Parlapani E, Rietschel M, Falkai P, Henn FA (2010) Gene expression of NMDA receptor subunits in the cerebellum of elderly patients with schizophrenia. Eur Arch Psychiatry Clin Neurosci 260(2):101–111

    Article  PubMed  Google Scholar 

  28. Sivagnanasundaram S, Crossett B, Dedova I, Cordwell S, Matsumoto I (2007) Abnormal pathways in the genu of the corpus callosum in schizophrenia pathogenesis: a proteome study. Proteomics Clin Appl 1:1291–1305

    Article  PubMed  CAS  Google Scholar 

  29. Stone JM (2009) Imaging the glutamate system in humans: relevance to drug discovery for schizophrenia. Curr Pharm Des 15(22):2594–2602

    Article  PubMed  CAS  Google Scholar 

  30. Tiedtke PI, Bischoff C, Schmidt WJ (1990) MK-801-induced stereotypy and its antagonism by neuroleptic drugs. J Neural Transm Gen Sect 81(3):173–182

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We would like to thank Dr. Giuseppina Maccarrone, Dr. Jeeva Varadarajulu, and Dr. Claudia Ditzen for the scientific discussion and advice. We also thank Jacquie Klesing, ELS, for editing assistance with the manuscript. The authors declare no competing interests.

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Authors and Affiliations

  1. Max Planck Institute of Psychiatry, Kraepelinstr. 2, 80804, Munich, Germany

    Daniel Martins-de-Souza, Maria Lebar & Christoph W. Turck

  2. Laboratório de Neurociências (LIM-27), Instituto de Psiquiatria, Faculdade de Medicina da USP, São Paulo, SP, CEP 05403-010, Brazil

    Daniel Martins-de-Souza

  3. Department of Chemical Engineering and Biotechnology, University of Cambridge, Tennis Court Road, Cambridge, CB 2 1QT, UK

    Daniel Martins-de-Souza

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  1. Daniel Martins-de-Souza
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  2. Maria Lebar
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  3. Christoph W. Turck
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Correspondence to Daniel Martins-de-Souza.

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Martins-de-Souza, D., Lebar, M. & Turck, C.W. Proteome analyses of cultured astrocytes treated with MK-801 and clozapine: similarities with schizophrenia. Eur Arch Psychiatry Clin Neurosci 261, 217–228 (2011). https://doi.org/10.1007/s00406-010-0166-2

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  • DOI: https://doi.org/10.1007/s00406-010-0166-2

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