title: Proteomics of the corpus callosum unravel pivotal players in the dysfunction of cell signaling, structure, and myelination in schizophrenia brains.
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.
authors.affiliation: Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Rua Monteiro Lobato, 255, Campinas, SP, 13083-862, Brazil.
authors.forename: Verônica M
authors.initials: VM
authors.lastname: Saia-Cereda
authors.affiliation: Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Rua Monteiro Lobato, 255, Campinas, SP, 13083-862, Brazil.
authors.forename: Juliana S
authors.initials: JS
authors.lastname: Cassoli
authors.affiliation: Laboratório de Neurociências (LIM-27), Instituto de Psiquiatria, Universidade de São Paulo, São Paulo, Brazil.|Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University (LMU), Munich, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Schmitt
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University (LMU), Munich, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Falkai
authors.affiliation: Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Rua Monteiro Lobato, 255, Campinas, SP, 13083-862, Brazil.|D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil.
authors.forename: Juliana M
authors.initials: JM
authors.lastname: Nascimento
authors.affiliation: Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Rua Monteiro Lobato, 255, Campinas, SP, 13083-862, Brazil. danms90@gmail.com.|Laboratório de Neurociências (LIM-27), Instituto de Psiquiatria, Universidade de São Paulo, São Paulo, Brazil. danms90@gmail.com.|UNICAMP's Neurobiology Center, Campinas, Brazil. danms90@gmail.com.
authors.forename: Daniel
authors.initials: D
authors.lastname: Martins-de-Souza
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D003337:Corpus Callosum / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009186:Myelin Sheath / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics; D012559:Schizophrenia / Q000378:metabolism*; D015398:Signal Transduction; D053719:Tandem Mass Spectrometry; D015854:Up-Regulation
chemical_list: D020543:Proteome
keywords: Corpus callosum; Mass spectrometry; Postmortem brain; Proteome; Proteomics; Schizophrenia