Proteomics of the corpus callosum unravel pivotal players in the dysfunction of cell signaling, structure, and myelination in schizophrenia brains

Autor(es)

Saia-Cereda, Veronica M. ^[1] ; Cassoli, Juliana S. ^[1] ; Schmitt, Andrea ^{[2, 3]} ; Falkai, Peter ^[3] ; Nascimento, Juliana M. ^{[4, 1]} ; Martins-de-Souza, Daniel ^{[1, 2, 5]}

Afiliação do(s) autor(es)

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

^[2] Univ Sao Paulo, Inst Psiquiatria, Lab Neurociencias LIM 27, Sao Paulo - Brazil

^[3] LMU, Dept Psychiat & Psychotherapy, Munich - Germany

^[4] DOr Inst Res & Educ IDOR, Rio De Janeiro - Brazil

^[5] UNICAMPs Neurobiol Ctr, Campinas - Brazil

• Tipo de documento: Artigo Científico
• Fonte: EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE; v. 265, n. 7, p. 601-612, OCT 2015.
• Citações Web of Science: 28

Resumo

Schizophrenia is an incurable and debilitating mental disorder that may affect up to 1 % of the world population. Morphological, electrophysiological, and neurophysiological studies suggest that the corpus callosum (CC), which is the largest portion of white matter in the human brain and responsible for inter-hemispheric communication, is altered in schizophrenia patients. Here, we employed mass spectrometry-based proteomics to investigate the molecular underpinnings of schizophrenia. Brain tissue samples were collected postmortem from nine schizophrenia patients and seven controls at the University of Heidelberg, Germany. Because the CC has a signaling role, we collected cytoplasmic (soluble) proteins and submitted them to nano-liquid chromatography-mass spectrometry (nano LC-MS/MS). Proteomes were quantified by label-free spectral counting. We identified 5678 unique peptides that corresponded to 1636 proteins belonging to 1512 protein families. Of those proteins, 65 differed significantly in expression: 28 were upregulated and 37 downregulated. Our data increased significantly the knowledge derived from an earlier proteomic study of the CC. Among the differentially expressed proteins are those associated with cell growth and maintenance, such as neurofilaments and tubulins; cell communication and signaling, such as 14-3-3 proteins; and oligodendrocyte function, such as myelin basic protein and myelin-oligodendrocyte glycoprotein. Additionally, 30 of the differentially expressed proteins were found previously in other proteomic studies in postmortem brains; this overlap in findings validates the present study and indicates that these proteins may be markers consistently associated with schizophrenia. Our findings increase the understanding of schizophrenia pathophysiology and may serve as a foundation for further treatment strategies. (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