Effect of MK-801 and clozapine on the proteome of cultured human oligodendrocytes

Separate lines of evidence have demonstrated the involvement of 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 t...

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Main Authors: Juliana Silva Cassoli, Keiko eIwata, Johann eSteiner, Paul C. Guest, Christoph W Turck, Juliana Minardi Nascimento, Daniel eMartins-de-Souza
Format: Article
Language:English
Published: Frontiers Media S.A. 2016-03-01
Series:Frontiers in Cellular Neuroscience
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fncel.2016.00052/full
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author Juliana Silva Cassoli
Keiko eIwata
Johann eSteiner
Paul C. Guest
Christoph W Turck
Juliana Minardi Nascimento
Juliana Minardi Nascimento
Daniel eMartins-de-Souza
Daniel eMartins-de-Souza
author_facet Juliana Silva Cassoli
Keiko eIwata
Johann eSteiner
Paul C. Guest
Christoph W Turck
Juliana Minardi Nascimento
Juliana Minardi Nascimento
Daniel eMartins-de-Souza
Daniel eMartins-de-Souza
author_sort Juliana Silva Cassoli
collection DOAJ
description Separate lines of evidence have demonstrated the involvement of 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-801effects. 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.
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spelling doaj.art-728d9b22cb9244f0a7c0bbe2bb1c488b2022-12-22T01:18:04ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022016-03-011010.3389/fncel.2016.00052174593Effect of MK-801 and clozapine on the proteome of cultured human oligodendrocytesJuliana Silva Cassoli0Keiko eIwata1Johann eSteiner2Paul C. Guest3Christoph W Turck4Juliana Minardi Nascimento5Juliana Minardi Nascimento6Daniel eMartins-de-Souza7Daniel eMartins-de-Souza8University of CampinasResearch 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 and University of Fukui, Fukui, Japan.University of MagdeburgUniversity of CampinasMax Planck Institute of PsychiatryUniversity of CampinasD’Or Institute for Research and Education (IDOR)University of CampinasUNICAMP Neurobiology CenterSeparate lines of evidence have demonstrated the involvement of 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-801effects. 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.http://journal.frontiersin.org/Journal/10.3389/fncel.2016.00052/fullClozapinePharmacologyProteomicsSchizophreniaoligodendrocyteglial cells
spellingShingle Juliana Silva Cassoli
Keiko eIwata
Johann eSteiner
Paul C. Guest
Christoph W Turck
Juliana Minardi Nascimento
Juliana Minardi Nascimento
Daniel eMartins-de-Souza
Daniel eMartins-de-Souza
Effect of MK-801 and clozapine on the proteome of cultured human oligodendrocytes
Frontiers in Cellular Neuroscience
Clozapine
Pharmacology
Proteomics
Schizophrenia
oligodendrocyte
glial cells
title Effect of MK-801 and clozapine on the proteome of cultured human oligodendrocytes
title_full Effect of MK-801 and clozapine on the proteome of cultured human oligodendrocytes
title_fullStr Effect of MK-801 and clozapine on the proteome of cultured human oligodendrocytes
title_full_unstemmed Effect of MK-801 and clozapine on the proteome of cultured human oligodendrocytes
title_short Effect of MK-801 and clozapine on the proteome of cultured human oligodendrocytes
title_sort effect of mk 801 and clozapine on the proteome of cultured human oligodendrocytes
topic Clozapine
Pharmacology
Proteomics
Schizophrenia
oligodendrocyte
glial cells
url http://journal.frontiersin.org/Journal/10.3389/fncel.2016.00052/full
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