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The role of hnRNPs in oligodendrocytes and their implications on schizophrenia

Grant number: 17/25055-3
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): August 01, 2018
Effective date (End): February 28, 2021
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Daniel Martins-de-Souza
Grantee:Caroline Brandão Teles
Home 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 severe, disabling and incurable mental disorder that affects about 0.7% of the world's population. Among the many hypotheses that attempt to explain the causes of schizophrenia, neurodevelopment suggests that a combination of genetic and environmental factors are fundamental in the onset of this disorder, usually in late adolescence / early adulthood. It has already been shown that there is a disconnection in the prefrontal cortex of patients with schizophrenia that has been associated with changes in the white matter, oligodendrocytes and myelin sheath. Myelin is produced only by mature oligodendrocytes, so a dysfunction during maturation of these cells could lead to a change in the normal processes of myelination, causing the hypomyelination observed in patients with schizophrenia. Still, recent studies in our group suggest the involvement of spliceosome in the disorder. Despite these findings, functional studies are necessary to better connect these different aspects of the disease, aiming to understand the pathophysiology of schizophrenia in an integrated way. In this context, the present project proposes to study the role of spliceosome in the maturation of oligodendrocytes and its relation with schizophrenia through the integration of transcriptomics and proteomics. In addition, we will evaluate the role of antipsychotics (haloperidol, clozapine and aripiprazole) in the spliceosome machinery in oligodendrocytes. The present study will contribute to a further step in understanding the pathophysiology of schizophrenia through the identification of pathways and key molecules of this disorder, which may serve as a target for the development of new and more effective treatments, improving the patient's quality of life.