Display options
Cite
Guest PC, Iwata K, Kato TA, et al. MK-801 treatment affects glycolysis in oligodendrocytes more than in astrocytes and neuronal cells: insights for schizophrenia. Front Cell Neurosci. 2015;9:180doi: 10.3389/fncel.2015.00180.
Guest, P. C., Iwata, K., Kato, T. A., Steiner, J., Schmitt, A., Turck, C. W., & Martins-de-Souza, D. (2015). MK-801 treatment affects glycolysis in oligodendrocytes more than in astrocytes and neuronal cells: insights for schizophrenia. Frontiers in cellular neuroscience, 9180. https://doi.org/10.3389/fncel.2015.00180
Guest, Paul C, et al. "MK-801 treatment affects glycolysis in oligodendrocytes more than in astrocytes and neuronal cells: insights for schizophrenia." Frontiers in cellular neuroscience vol. 9 (2015): 180. doi: https://doi.org/10.3389/fncel.2015.00180
Guest PC, Iwata K, Kato TA, Steiner J, Schmitt A, Turck CW, Martins-de-Souza D. MK-801 treatment affects glycolysis in oligodendrocytes more than in astrocytes and neuronal cells: insights for schizophrenia. Front Cell Neurosci. 2015 May 12;9:180. doi: 10.3389/fncel.2015.00180. eCollection 2015. PMID: 26029051; PMCID: PMC4429244.
Copy Download .nbib Format: NLM
Share it on

Front Cell Neurosci. 2015 May 12;9:180. doi: 10.3389/fncel.2015.00180. eCollection 2015.

MK-801 treatment affects glycolysis in oligodendrocytes more than in astrocytes and neuronal cells: insights for schizophrenia.

Frontiers in cellular neuroscience

Paul C Guest, Keiko Iwata, Takahiro A Kato, Johann Steiner, Andrea Schmitt, Christoph W Turck, Daniel Martins-de-Souza

Affiliations

  1. Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas Campinas, Brazil.
  2. Research Center for Child Mental Development, University of Fukui Fukui, Japan ; Department of Development of Functional Brain Activities, United Graduate School of Child Development, Osaka University-Kanazawa University-Hamamatsu University School of Medicine-Chiba University-University of Fukui Fukui, Japan.
  3. Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University Fukuoka, Japan ; Innovation Center for Medical Redox Navigation, Kyushu University Fukuoka, Japan.
  4. Department of Psychiatry and Psychotherapy-Center for Behavioral Brain Sciences, University of Magdeburg Magdeburg, Germany.
  5. Department of Psychiatry and Psychotherapy, Ludwig-Maximilians University Munich, Germany ; Laboratory of Neurosciences (LIM-27), Institute of Psychiatry, University of São Paulo São Paulo, Brazil.
  6. Department of Translational Research in Psychiatry Proteomics and Biomarkers, Max Planck Institute of Psychiatry Munich, Germany.
  7. Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas Campinas, Brazil ; Laboratory of Neurosciences (LIM-27), Institute of Psychiatry, University of São Paulo São Paulo, Brazil ; UNICAMP's Neurobiology Center Campinas, Brazil.

PMID: 26029051 PMCID: PMC4429244 DOI: 10.3389/fncel.2015.00180

Abstract

Schizophrenia is a debilitating mental disorder, affecting more than 30 million people worldwide. As a multifactorial disease, the underlying causes of schizophrenia require analysis by multiplex methods such as proteomics to allow identification of whole protein networks. Previous post-mortem proteomic studies on brain tissues from schizophrenia patients have demonstrated changes in activation of glycolytic and energy metabolism pathways. However, it is not known whether these changes occur in neurons or in glial cells. To address this question, we treated neuronal, astrocyte, and oligodendrocyte cell lines with the NMDA receptor antagonist MK-801 and measured the levels of six glycolytic enzymes by Western blot analysis. MK-801 acts on the glutamatergic system and has been proposed as a pharmacological means of modeling schizophrenia. Treatment with MK-801 resulted in significant changes in the levels of glycolytic enzymes in all cell types. Most of the differences were found in oligodendrocytes, which had altered levels of hexokinase 1 (HK1), enolase 2 (ENO2), phosphoglycerate kinase (PGK), and phosphoglycerate mutase 1 after acute MK-801 treatment (8 h), and HK1, ENO2, PGK, and triosephosphate isomerase (TPI) following long term treatment (72 h). Addition of the antipsychotic clozapine to the cultures resulted in counter-regulatory effects to the MK-801 treatment by normalizing the levels of ENO2 and PGK in both the acute and long term cultures. In astrocytes, MK-801 affected only aldolase C (ALDOC) under both acute conditions and HK1 and ALDOC following long term treatment, and TPI was the only enzyme affected under long term conditions in the neuronal cells. In conclusion, MK-801 affects glycolysis in oligodendrocytes to a larger extent than neuronal cells and this may be modulated by antipsychotic treatment. Although cell culture studies do not necessarily reflect the in vivo pathophysiology and drug effects within the brain, these results suggest that neurons, astrocytes, and oligodendrocytes are affected differently in schizophrenia. Employing in vitro models using neurotransmitter agonists and antagonists may provide new insights about the pathophysiology of schizophrenia which could lead to a novel system for drug discovery.

Keywords: MK-801; Western blot; astrocytes; clozapine; glycolysis; neurons; oligodendrocytes; schizophrenia

References

  1. J Neurosci Res. 2015 Jul;93(7):999-1008 - PubMed
  2. Neuropsychopharmacology. 2006 Sep;31(9):1880-7 - PubMed
  3. J Psychiatr Res. 2012 Jan;46(1):95-104 - PubMed
  4. J Immunol. 2007 May 15;178(10):6549-56 - PubMed
  5. Prog Neuropsychopharmacol Biol Psychiatry. 2013 Aug 1;45:100-6 - PubMed
  6. Annu Rev Cell Dev Biol. 2014;30:503-33 - PubMed
  7. Eur Arch Psychiatry Clin Neurosci. 2011 Apr;261(3):217-28 - PubMed
  8. Proteomics. 2009 Jun;9(12):3368-82 - PubMed
  9. J Proteome Res. 2010 Sep 3;9(9):4346-55 - PubMed
  10. Acta Neuropathol. 2009 Apr;117(4):395-407 - PubMed
  11. Front Cell Neurosci. 2014 Nov 18;8:384 - PubMed
  12. J Psychiatr Res. 2011 Feb;45(2):273-9 - PubMed
  13. Schizophr Res. 2015 Jan;161(1):85-93 - PubMed
  14. World J Biol Psychiatry. 2013 Sep;14(7):478-89 - PubMed
  15. Arch Gen Psychiatry. 2011 May;68(5):477-88 - PubMed
  16. Neuron. 1997 Aug;19(2):453-63 - PubMed
  17. J Cereb Blood Flow Metab. 2011 Mar;31(3):976-85 - PubMed
  18. Int J Obes. 1979;3(4):301-23 - PubMed
  19. Clin Chem. 2010 Dec;56(12):1804-13 - PubMed
  20. Antioxid Redox Signal. 2011 Oct 1;15(7):2067-79 - PubMed
  21. Biol Psychiatry. 2011 Jan 15;69(2):163-72 - PubMed
  22. Mol Psychiatry. 2008 Dec;13(12):1102-17 - PubMed
  23. J Psychiatr Res. 2010 Feb;44(3):149-56 - PubMed
  24. J Neurobiol. 1995 Feb;26(2):283-93 - PubMed
  25. BMC Res Notes. 2012 Mar 15;5:146 - PubMed
  26. Nature. 2012 Jul 26;487(7408):443-8 - PubMed
  27. PLoS One. 2010 Dec 16;5(12 ):e15230 - PubMed
  28. Neuroscience. 2014 Sep 26;277:522-40 - PubMed
  29. Cell Physiol Biochem. 2007;20(6):687-702 - PubMed
  30. Eur Arch Psychiatry Clin Neurosci. 2015 Mar;265(2):87-106 - PubMed
  31. Schizophr Res. 2015 Jan;161(1):4-18 - PubMed
  32. J Neurocytol. 2003 Jan;32(1):25-38 - PubMed
  33. Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):14040-5 - PubMed
  34. Nat Rev Drug Discov. 2006 Apr;5(4):271 - PubMed
  35. J Pharm Biomed Anal. 2011 May 15;55(2):373-8 - PubMed
  36. Endocrinol Metab Clin North Am. 2013 Sep;42(3):545-63 - PubMed
  37. J Neural Transm (Vienna). 2007 Jul;114(7):885-91 - PubMed
  38. Lancet. 2009 Aug 22;374(9690):635-45 - PubMed
  39. Eur Arch Psychiatry Clin Neurosci. 2013 Aug;263(5):367-77 - PubMed
  40. PLoS One. 2014 Oct 21;9(10):e110804 - PubMed
  41. Psychopharmacology (Berl). 2011 Feb;213(2-3):289-305 - PubMed
  42. Neuroscience. 2013 Jan 3;228:200-14 - PubMed
  43. Mol Psychiatry. 2011 Dec;16(12):1189-202 - PubMed
  44. Expert Rev Proteomics. 2012;9(1):97-108 - PubMed
  45. Eur Arch Psychiatry Clin Neurosci. 2014 Nov;264 Suppl 1:S67-82 - PubMed
  46. Schizophr Bull. 2009 May;35(3):509-27 - PubMed

Publication Types