Effect of MK-801 and Clozapine on the Proteome of Cultured Human Oligodendrocytes

Author(s)

Cassoli, Juliana S. ^[1] ; Iwata, Keiko ^{[2, 3, 4, 5, 6]} ; Steiner, Johann ^[7] ; Guest, Paul C. ^[1] ; Turck, Christoph W. ^[8] ; Nascimento, Juliana M. ^{[9, 1]} ; Martins-de-Souza, Daniel ^{[1, 10]}

Affiliation

^[1] Univ Estadual Campinas, Lab Neuroprote, Dept Biochem & Tissue Biol, Inst Biol, Campinas, SP - Brazil

^[2] Hamamatsu Univ Sch Med, United Grad Sch Child Dev, Dept Dev Funct Brain Activ, Res Ctr Child Mental Dev, Hamamatsu, Shizuoka - Japan

^[3] Osaka Univ, Suita, Osaka 565 - Japan

^[4] Kanazawa Univ, Kanazawa, Ishikawa 9201192 - Japan

^[5] Chiba Univ, Chiba - Japan

^[6] Univ Fukui, Fukui 910 - Japan

^[7] Univ Magdeburg, Dept Psychiat, D-39106 Magdeburg - Germany

^[8] Max Planck Inst Psychiat, Dept Translat Res Psychiat, Munich - Germany

^[9] DOr Inst Res & Educ, Rio De Janeiro - Brazil

^[10] Univ Estadual Campinas, Neurobiol Ctr, Campinas, SP - Brazil

• Document type: Journal article
• Source: FRONTIERS IN CELLULAR NEUROSCIENCE; v. 10, MAR 3 2016.
• Web of Science Citations: 14

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. (AU)

• FAPESP's process: 14/21035-0 - Quantitative proteomics in neural cell lines and organoids derived from induced pluripotent stem cells from schizophrenia patients
• Grantee: Juliana Minardi Nascimento
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 14/10068-4 - Multi-User Equipment approved in grant 13/08711-3: mass spectrometer waters SYNAPT G2-Si HDMS + nanoACQUITY UPLC
• Grantee: Daniel Martins-de-Souza
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 14/14881-1 - Understanding the influence of glycolysis components in the function of oligodendrocytes: linking with findings in schizophrenia
• Grantee: Juliana Silva Cassoli
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/08711-3 - Developing a predictive test for a successful medication response and understanding the molecular bases of schizophrenia through proteomics
• Grantee: Daniel Martins-de-Souza
• Support Opportunities: Research Grants - Young Investigators Grants