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

Autor(es)

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]}

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN CELLULAR NEUROSCIENCE; v. 10, MAR 3 2016.
• Citações Web of Science: 14

Resumo

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)

• Processo FAPESP: 14/21035-0 - Proteômica quantitativa de linhagens neurais e organóides cerebrais derivados de células tronco de pluripotência induzida de pacientes com esquizofrenia
• Beneficiário: Juliana Minardi Nascimento
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 14/10068-4 - EMU concedido no processo 13/08711-3: espectrômetro de massas Waters SYNAPT G2-Si HDMs + nanoACQUITY UPLC
• Beneficiário: Daniel Martins-de-Souza
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
• Processo FAPESP: 14/14881-1 - Compreensão da influência de componentes da via glicolítica na função dos oligodendrócitos: uma relação com os achados em esquizofrenia
• Beneficiário: Juliana Silva Cassoli
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 13/08711-3 - Desenvolvimento de um teste preditivo para medicação bem sucedida e compreensão das bases moleculares da esquizofrenia através da proteômica
• Beneficiário: Daniel Martins-de-Souza
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores