title: Effect of MK-801 and Clozapine on the Proteome of Cultured Human Oligodendrocytes.
abstract: Separate lines of evidence have demonstrated the involvement of N-methyl-D-aspartate (NMDA) receptor and oligodendrocyte dysfunctions in schizophrenia. Here, we have carried out shotgun mass spectrometry proteome analysis of oligodendrocytes treated with the NMDA receptor antagonist MK-801 to gain potential insights into these effects at the molecular level. The MK-801 treatment led to alterations in the levels of 68 proteins, which are associated with seven distinct biological processes. Most of these proteins are involved in energy metabolism and many have been found to be dysregulated in previous proteomic studies of post-mortem brain tissues from schizophrenia patients. Finally, addition of the antipsychotic clozapine to MK-801-treated oligodendrocyte cultures resulted in changes in the levels of 45 proteins and treatment with clozapine alone altered 122 proteins and many of these showed opposite changes to the MK-801 effects. Therefore, these proteins and the associated energy metabolism pathways should be explored as potential biomarkers of antipsychotic efficacy. In conclusion, MK-801 treatment of oligodendrocytes may provide a useful model for testing the efficacy of novel treatment approaches.
authors.affiliation: Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas Campinas, Brazil.
authors.forename: Juliana S
authors.initials: JS
authors.lastname: Cassoli
authors.affiliation: United Graduate School of Child Development, Department of Development of Functional Brain Activities, Research Center for Child Mental Development, Hamamatsu University School of Medicine, Osaka University and Kanazawa University and Chiba University and University of Fukui Fukui, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Iwata
authors.affiliation: Department of Psychiatry, University of Magdeburg Magdeburg, Germany.
authors.forename: Johann
authors.initials: J
authors.lastname: Steiner
authors.affiliation: Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas Campinas, Brazil.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Guest
authors.affiliation: Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry Munich, Germany.
authors.forename: Christoph W
authors.initials: CW
authors.lastname: Turck
authors.affiliation: Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of CampinasCampinas, Brazil; D'Or Institute for Research and Education Rio de Janeiro, Brazil.
authors.forename: Juliana M
authors.initials: JM
authors.lastname: Nascimento
authors.affiliation: Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of CampinasCampinas, Brazil; UNICAMP Neurobiology CenterCampinas, Brazil.
authors.forename: Daniel
authors.initials: D
authors.lastname: Martins-de-Souza
keywords: MK801; clozapine; glial cells; oligodendrocyte; pharmacology; proteomics; schizophrenia