Ubiquitin-proteasome system, lipid metabolism and DNA damage repair are triggered by antipsychotic medication in human oligodendrocytes: implications in schizophrenia

Autor(es)

Seabra, Gabriela ^[1] ; de Almeida, Valeria ^[1] ; Reis-de-Oliveira, Guilherme ^[1] ; Crunfli, Fernanda ^[1] ; Leao Marcelo Antunes, Andre Saraiva ^[1] ; Martins-de-Souza, Daniel ^{[1, 2, 3]}

Afiliação do(s) autor(es)

^[1] Univ Campinas UNICAMP, Inst Biol, Dept Biochem & Tissue Biol, Lab Neuroprote, Rua Monteiro Lobato 255, BR-13083862 Campinas, SP - Brazil

^[2] DOr Inst Res & Educ IDOR, Sao Paulo - Brazil

^[3] Univ Estadual Campinas, Expt Med Res Cluster EMRC, Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 10, n. 1 JUL 28 2020.
• Citações Web of Science: 0

Resumo

Schizophrenia is a chronic, severe and disabling psychiatric disorder, whose treatment is based on psychosocial interventions and the use of antipsychotic drugs. While the effects of these drugs are well elucidated in neuronal cells, they are still not so clear in oligodendrocytes, which play a vital role in schizophrenia. Thus, we aimed to characterize biochemical profiles by proteomic analyses of human oligodendrocytes (MO3.13) which were matured using a protocol we developed and treated with either haloperidol (a typical antipsychotic), clozapine (an atypical antipsychotic) or a clozapine+d-serine co-treatment, which has emerged lately as an alternative type of treatment. This was accomplished by employing shotgun proteomics, using nanoESI-LC-MS/MS label-free quantitation. Proteomic analysis revealed biochemical pathways commonly affected by all tested antipsychotics were mainly associated to ubiquitination, proteasome degradation, lipid metabolism and DNA damage repair. Clozapine and haloperidol treatments also affected proteins involved with the actin cytoskeleton and with EIF2 signaling. In turn, metabolic processes, especially the metabolism of nitrogenous compounds, were a predominant target of modulation of clozapine+d-serine treatment. In this context, we seek to contribute to the understanding of the biochemical and molecular mechanisms involved in the action of antipsychotics on oligodendrocytes, along with their possible implications in schizophrenia. (AU)

• Processo FAPESP: 19/22398-2 - O papel da síntese de colesterol no mecanismo de ação da clozapina em modelos experimentais para esquizofrenia
• Beneficiário: Fernanda Crunfli
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 17/25588-1 - Da compreensão básica a biomarcadores clínicos para a esquizofrenia: um estudo multidisciplinar centrado na neuroproteômica
• Beneficiário: Daniel Martins-de-Souza
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• 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: 17/18242-1 - Vias bioquímicas moduladas por drogas canabinóides em oligodendrócitos humanos
• Beneficiário: Valéria de Almeida
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 19/03271-1 - Modulação do proteoma por drogas canabinóides em oligodendrócitos humanos
• Beneficiário: Gabriela Seabra
• Modalidade de apoio: Bolsas no Brasil - Programa Capacitação - Treinamento Técnico
• Processo FAPESP: 19/00098-7 - EMU concedido no processo 2017/25588-1: cromatógrafo Acquity UPLC I-Class
• Beneficiário: Daniel Martins-de-Souza
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
• Processo FAPESP: 18/03673-0 - Efeitos bioquímicos de canabinóides em oligodendrócitos: implicações para a esquizofrenia
• Beneficiário: Daniel Martins-de-Souza
• Modalidade de apoio: Auxílio à Pesquisa - Regular