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

Author(s)

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]}

Affiliation

^[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

• Document type: Journal article
• Source: EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE; v. 265, n. 7, p. 601-612, OCT 2015.
• Web of Science Citations: 28

Abstract

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)

• 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