Digging deeper in the proteome of different regions from schizophrenia brains

Autor(es)

Reis-de-Oliveira, G. ^[1] ; Zuccoli, G. S. ^{[1, 2]} ; Fioramonte, M. ^{[1, 2]} ; Schimitt, A. ^{[3, 4]} ; Falkai, P. ^[4] ; Almeida, V ^{[1, 2]} ; Martins-de-Souza, D. ^{[5, 1, 6, 7, 2]}

Afiliação do(s) autor(es)

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

^[2] Schimitt, A., Univ Sao Paulo, Inst Psychiat, Lab Neurosci LIM 27, Sao Paulo, Brazil.Reis-de-Oliveira, G., Univ Estadual Campinas, Inst Biol, Dept Biochem & Tissue Biol, Lab Neuroprote, UNICAMP, Campinas, SP - Brazil

^[3] Univ Sao Paulo, Inst Psychiat, Lab Neurosci LIM 27, Sao Paulo - Brazil

^[4] Ludwig Maximilian Univ LMU, Dept Psychiat & Psychotherapy, Munich - Germany

^[5] Conselho Nacl Desenvolvimento Cient & Tecnol, Inst Nacl Biomarcadores Neuropsiquiatria INBION, Sao Paulo - Brazil

^[6] DOr Inst Res & Educ IDOR, Sao Paulo - Brazil

^[7] Univ Estadual Campinas, Expt Med Res Cluster EMRC, Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF PROTEOMICS; v. 223, JUL 15 2020.
• Citações Web of Science: 1

Resumo

Schizophrenia is a psychiatric disorder that affects 21 million people worldwide. Despite several studies having been shown that some brain regions may play a critical role in the pathophysiology o f schizophrenia, the mo lecular basis to explain this diversity is still lacking. The cerebellum (CER), caudate nucleus (CAU), and posterior cingulate cortex (PCC) are areas associated with negative and cognitive symptoms in schizophrenia. In this study, w e performed shotgun proteomics o f the aforementioned brain regions, collected postmortem from pa tients with schizophrenia and compared with the mentally healthy group. In addition, w e performed a proteomic analysis o f nuclear and mitochondrial fractions of these same regions. Our results presented 106, 727 and 135 differentially regulated proteins in the CAU, PCC, and CER, respectively. Pathway enrichment analysis revealed dysfunctions associated with synaptic processes in the CAU, transport in the CER, and in energy metabolism in the PCC. In all brain areas, w e found that proteins related to oligodendrocytes and the metabolic processes were dysregulated in schizophrenia. Significance: Schizophrenia is a complex and heterogeneous psychiatric disorder. Despite much research having been done to increase the knowledge about the role o f each region in the pathophysiology o f this disorder, the molecular mechanisms underlying it are still lacking. We performed shotgun proteomics in the postmortem cerebellum (CER), caudate nucleus (CAU) and posterior cingulate cortex (PCC) from patients with schizophrenia and compared with healthy controls. Our findings suggest that each aforementioned region presents dysregulations in specific molecular pathways, such as energy metabolism in the PCC, transport in the CER, and synaptic process in the CAU. Additionally, these areas presented dysfunctions in oligodendrocytes and metabolic processes. Our results may highlight future directions for the development of novel clinical approaches for specific therapeutic targets. (AU)

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