Investigation of the role of hnrnps in remyelination in the context of cuprizone-induced demyelination

Author(s)

Caroline Brandão Teles

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2024-02-07

Examining board members

Daniel Martins de Souza; Carolina Demarchi Munhoz; Lisiane de Oliveira Porciúncula; Andre Schwambach Vieira; Vanessa Costhek Abílio

• Advisor: Daniel Martins de Souza

Abstract

The oligodendrocytes constitute the main cells responsible for myelin sheath production both in neurodevelopment and the adult brain. Myelin is produced only by mature oligodendrocytes, so dysfunction during the maturation of these cells could lead to alterations in normal myelination processes, causing the hypomyelination observed in schizophrenia patients. Proteins belonging to the heterogeneous nuclear ribonucleoprotein (hnRNP) family, such as hnRNP K, seem to play a significant role in myelin basic protein (MBP) synthesis. Changes in these proteins have been reported in different schizophrenia studies, indicating a possible role in the observed myelin dysfunctions in the disorder. Recent studies from our group suggest the involvement of these proteins not only in the disease but also in its treatment. Despite these findings, functional studies are necessary to better connect these different aspects of the disease, aiming to understand schizophrenia's pathophysiology in an integrated manner. Given the context of the role of oligodendrocytes in schizophrenia's pathophysiology, the objective of this project is to evaluate the role of hnRNPs in the myelination process through in vivo and in vitro experimental models for schizophrenia. To achieve this, the following models were used: the demyelination model, in which mice were exposed to Cuprizone, followed by treatment with a pharmacological inhibitor of hnRNP A1 protein splicing activity (VPC-80051). Additionally, we assessed the relationship between hnRNP A1 activity and the myelination process through proteomic and molecular analysis. Thus, this project will contribute to a better understanding of the role of hnRNPs in myelination and their relationships with schizophrenia, serving as targets for further studies and contributing to the development of more effective treatments (AU)

• FAPESP's process: 17/25055-3 - The role of hnRNPs in oligodendrocytes and their implications on schizophrenia
• Grantee: Caroline Brandão Teles Rodrigues
• Support Opportunities: Scholarships in Brazil - Doctorate