Employing human oligodendroglial cell cultures and glutamatergic dysfunction to understand the molecular basis of schizophrenia

• Grant number: 15/23049-0
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): March 01, 2016
• Effective date (End): February 28, 2018
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Daniel Martins-de-Souza
• Grantee: Caroline Brandão Teles Rodrigues
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 13/08711-3 - Developing a predictive test for a successful medication response and understanding the molecular bases of schizophrenia through proteomics, AP.JP

Abstract

Schizophrenia is a chronic mental illness that affects over 1% of world's population, being its development related to genetic factors. Cognitive disorders such as attention, memory and execu-tive functions are frequently observed in patients with the disease. The diagnosis is still essenti-ally clinical and the only way to control the symptoms is through the use of antipsychotics, which have notable side effects, mainly due to the lack of understanding of the molecular me-chanisms of this pathology. Proteome studies, which investigate the protein expression levels of the cell, as well as their post-translational modifications (phosphoproteome), have been used to identify biomarker candidates for schizophrenia. These could be useful in diagnosis, and can provide insights into the molecular basis of this disease's pathophysiology. Among all leads pro-posed by proteomic studies, the dysfunction of the oligodendrocytes, the myelinating cells of the central nervous system of the disease is notable. This project aims to characterize the proteome and the phosphoproteome of a cell line from human oligodendrocytes (MO3.13 cells) treated with MK-801, an antagonist of NMDA receptors, given its role on glutamatergic transmission, which is pivotal to schizophrenia. The molecular effects of clozapine, one of the most used anti-psychotic drugs will also be investigated on these cells. Obtained data will be compared to previ-ous findings in oligodendrocytes' cultures not treated with MK-801 and to the proteomic results of human brains collected postmortem from schizophrenia patients. Our aim is to unravel key proteins and molecular pathways possibly involved in schizophrenia´s pathogenic process. These proteins and pathways warrant further investigations as they can indicate new relevant therapeu-tic targets to schizophrenia.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

NASCIMENTO, JULIANA M.; GARCIA, SHEILA; SAIA-CEREDA, VERONICA M.; SANTANA, ALINE G.; BRANDAO-TELES, CAROLINE; ZUCCOLI, GIULIANA S.; JUNQUEIRA, DANIELLE G.; REIS-DE-OLIVEIRA, GUILHERME; BALDASSO, PAULO A.; CASSOLI, JULIANA S.; et al. Proteomics and molecular tools for unveiling missing links in the biochemical understanding of schizophrenia. PROTEOMICS CLINICAL APPLICATIONS, v. 10, n. 12, SI, p. 1148-1158, DEC 2016. (14/14881-1, 15/23049-0, 16/04912-2, 13/08711-3, 14/21035-0)

BRANDAO-TELES, CAROLINE; DE ALMEIDA, VALERIA; CASSOLI, JULIANA S.; MARTINS-DE-SOUZA, DANIEL. Oligodendrocytes: Potential of Discovering New Treatment Targets. FRONTIERS IN PHARMACOLOGY, v. 10, MAR 5 2019. (17/25588-1, 14/14881-1, 15/23049-0, 17/18242-1, 14/10068-4)

CASSOLI, JULIANA S.; BRANDAO-TELES, CAROLINE; SANTANA, ALINE G.; SOUZA, GUSTAVO H. M. F.; MARTINS-DE-SOUZA, DANIEL. Ion Mobility-Enhanced Data-Independent Acquisitions Enable a Deep Proteomic Landscape of Oligodendrocytes. PROTEOMICS, v. 17, n. 21, NOV 2017. (15/23049-0, 14/14881-1, 13/08711-3, 14/10068-4)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

RODRIGUES, Caroline Brandão Teles. Employing proteomics to understand the mechanisms of action of antipsychotics in human oligodendrocytes. 2018. Master's Dissertation - Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia Campinas, SP.