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Effect of the atypical neuroleptic risperidone on morphology and S100B secretion in C6 astroglial lineage cells

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Abstract

We investigated the effect of the atypical neuroleptic risperidone on morphology and S100B secretion in C6 glioma cells, considering the putative involvement of astroglial cells in neuropsychiatric disorders. In the presence of high experimental doses of risperidone, C6 cells become stellate, with process-bearing cells and partial retraction of the cell body followed by detachment from the adhesion surface with practically no cell death. These results indicate that risperidone is able to interfere with C6 cell adhesion without toxic effects. RhoA activator LPA prevented the effects of risperidone on cell morphology. From 6 h risperidone induced a statistically significant increment of about 80% in S100B secretion. These data contribute to the proposal that glial cells are targets of risperidone, which could be involved in the therapeutic response of risperidone to improve autism symptoms.

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References

  1. De Deyn PP, Buitelaar J (2006) Risperidone in the management of agitation and aggression associated with psychiatric disorders. Eur Psychiatry 21:21–28

    Article  PubMed  Google Scholar 

  2. Gaspar P, Cases O, Maroteaux L (2003) The developmental role of serotonin: news from mouse molecular genetics. Nat Rev Neurosci 4:1002–1012

    Article  PubMed  CAS  Google Scholar 

  3. Scott LJ, Dhillon S (2007) Risperidone: a review of its use in the treatment of irritability associated with autistic disorder in children and adolescents. Paediatr Drugs 9:343–354

    Article  PubMed  Google Scholar 

  4. Murcia CL, Gulden F, Herrup K (2005) A question of balance: a proposal for new mouse models of autism. Int J Dev Neurosci 23:265–275

    Article  PubMed  Google Scholar 

  5. Minshew NJ, Williams DL (2007) The new neurobiology of autism: cortex, connectivity, and neuronal organization. Arch Neurol 64:945–950

    Article  PubMed  Google Scholar 

  6. Rothermundt M, Ponath G, Arolt V (2004) S100B in schizophrenic psychosis. Int Rev Neurobiol 59:445–470

    PubMed  CAS  Google Scholar 

  7. Leite M, Frizzo JK, Nardin P, de Almeida LM, Tramontina F, Gottfried C, Gonçalves CA (2004) Beta-hydroxy-butyrate alters the extracellular content of S100B in astrocyte cultures. Brain Res Bull 64:139–143

    Article  PubMed  CAS  Google Scholar 

  8. Van Eldik LJ, Wainwright MS (2003) The Janus face of glial-derived S100B: beneficial and detrimental functions in the brain. Restor Neurol Neurosci 21:97–108

    PubMed  Google Scholar 

  9. Ahlemeyer B, Beier H, Semkova I, Schaper C, Krieglstein J (2000) S-100beta protects cultured neurons against glutamate- and staurosporine-induced damage and is involved in the antiapoptotic action of the 5 HT(1A)-receptor agonist, Bay x 3702. Brain Res 858:121–128

    Article  PubMed  CAS  Google Scholar 

  10. Pillai A, Terry AV Jr, Mahadik SP (2006) Differential effects of long-term treatment with typical and atypical antipsychotics on NGF and BDNF levels in rat striatum and hippocampus. Schizophr Res 82:95–106

    Article  PubMed  Google Scholar 

  11. Mangoura D, Sakellaridis N, Jones J, Vernadakis A (1989) Early and late passage C-6 glial cell growth: similarities with primary glial cells in culture. Neurochem Res 14:941–947

    Article  PubMed  CAS  Google Scholar 

  12. Cechin SR, Dunkley PR, Rodnight R (2005) Signal transduction mechanisms involved in the proliferation of C6 glioma cells induced by lysophosphatidic acid. Neurochem Res 30:603–611

    Article  PubMed  CAS  Google Scholar 

  13. Funchal C, Latini A, Jacques-Silva MC, Dos Santos AQ, Buzin L, Gottfried C, Wajner M, Pessoa-Pureur R (2006) Morphological alterations and induction of oxidative stress in glial cells caused by the branched-chain alpha-keto acids accumulating in maple syrup urine disease. Neurochem Int 49:640–650

    Article  PubMed  CAS  Google Scholar 

  14. Quincozes-Santos A, Andreazza AC, Nardin P, Funchal C, Gonçalves CA, Gottfried C (2007) Resveratrol attenuates oxidative-induced DNA damage in C6 Glioma cells. Neurotoxicology 28:886–891

    Article  PubMed  CAS  Google Scholar 

  15. Lowry OH, Rosenbrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin-Phenol reagents. J Biol Chem 193:265–275

    PubMed  CAS  Google Scholar 

  16. Cechin SR, Gottfried C, Prestes CC, Andrighetti L, Wofchuk ST, Rodnight R (2002) Astrocyte stellation in saline media lacking bicarbonate: possible relation to intracellular pH and tyrosine phosphorylation. Brain Res 946:12–23

    Article  PubMed  CAS  Google Scholar 

  17. Dos Santos AQ, Nardin P, Funchal C, de Almeida LM, Jacques-Silva MC, Wofchuk ST, Gonçalves CA, Gottfried C (2006) Resveratrol increases glutamate uptake and glutamine synthetase activity in C6 glioma cells. Arch Biochem Biophys 453:161–167

    Article  PubMed  CAS  Google Scholar 

  18. Leite MC, Galland F, Brolese G, Gerra MC, Bortolotto JW, Freitas R, de Almeida LM, Gottfried C, Gonçalves CA (2008) A simple, sensitive and widely applicable ELISA for S100B: methodological features of the measurement of this glial protein. J Neurosci Method 169:93–99

    CAS  Google Scholar 

  19. Aspenström P, Fransson A, Saras J (2004) Rho GTPases have diverse effects on the organization of the actin filament system. Biochem J 377:327–337

    Article  PubMed  Google Scholar 

  20. Ridley AJ (2006) Rho GTPases and actin dynamics in membrane protrusions and vesicle trafficking. Trends Cell Biol 16:522–529

    Article  PubMed  CAS  Google Scholar 

  21. Donato R (2001) S100: a multigenic family of calcium-modulated proteins of the EF-hand type with intracellular and extracellular functional roles. Int J Biochem Cell Biol 33:637–668

    Article  PubMed  CAS  Google Scholar 

  22. Tramontina F, Tramontina AC, Souza DF, Leite MC, Gottfried C, Souza DO, Wofchuk ST, Goncalves CA (2006) Glutamate uptake is stimulated by extracellular S100B in hippocampal astrocytes. Cell Mol Neurobiol 26:81–86

    PubMed  Google Scholar 

  23. Winningham-Major F, Staecker JL, Barger SW, Coats S, Van Eldik LJ (1089) Neurite extension and neuronal survival activities of recombinant S100 beta proteins that differ in the content and position of cysteine residues. J Cell Biol 109:3063–3071

    Article  Google Scholar 

  24. McDougle CJ, Erickson CA, Stigler KA, Posey DJ (2005) Neurochemistry in the pathophysiology of autism. Clin Psychiatry 66(Suppl 10):9–18

    CAS  Google Scholar 

  25. Santangelo SL, Tsatsanis K (2005) What is known about autism: genes, brain, and behavior. Am J Pharmacogenomics 5:71–92

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), and FINEP/ Rede IBN 01.06.0842–00. We would like to thank Ms. Alessandra Heizelmann for technical support with cell culture.

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Correspondence to Carmem Gottfried.

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Quincozes-Santos, A., Abib, R.T., Leite, M.C. et al. Effect of the atypical neuroleptic risperidone on morphology and S100B secretion in C6 astroglial lineage cells. Mol Cell Biochem 314, 59–63 (2008). https://doi.org/10.1007/s11010-008-9765-x

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  • DOI: https://doi.org/10.1007/s11010-008-9765-x

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