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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Format: | Article |
Language: | English |
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Frontiers Media S.A.
2016-03-01
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Series: | Frontiers in Cellular Neuroscience |
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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. |
first_indexed | 2024-12-11T06:12:23Z |
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institution | Directory Open Access Journal |
issn | 1662-5102 |
language | English |
last_indexed | 2024-12-11T06:12:23Z |
publishDate | 2016-03-01 |
publisher | Frontiers Media S.A. |
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series | Frontiers in Cellular Neuroscience |
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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