Investigating the particularities of atypical antipsychotics by assessing the oligodendrocyte secretome

• Grant number: 22/16373-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2023
• End date: January 31, 2024
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Daniel Martins-de-Souza
• Grantee: Caio Henrique de Souza Ferreira Berdeville
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 17/25588-1 - From the basic understanding to clinical biomarkers to schizophrenia: a neuroproteomics-centered multidisciplinary study, AP.TEM

Abstract

Schizophrenia, which affects almost 200 million people, is characterized by positive symptoms, such as hallucinations. It is understood that these patients exhibit exacerbations on subcortical dopamine circuits and hypoactivation on cortical. The treatment consists of the administration of antipsychotics, which antagonize D2 receptors but, if atypical, also block the 5-HT2A receptors. Although atypical antipsychotics present similar efficacy in the management of psychotic episodes, some specificities of those medications exert an important impact on drug selection. As an example, quetiapine leads to considerable sedation, olanzapine induces several weight gains, and clozapine is not only capable of managing threat-resistant schizophrenia but also reducing convulsive limiar. Thus, this project's objective is to investigate the particularities of the antipsichotics quetiapine, olanzapine, and clozapine based on the secretome of the cell line oligodendrocytes MO3.13, applying proteomic and metabolomic analysis. In order to reach this objective, immunocytochemistry will be applied to evaluate the expression of the D2 receptor on the cells, and drug doses will be determined by a 24-hour threat assessment followed by an MTT cell viability assay. After incubation, culture mediums will be analyzed by proteomic and metabolomic analysis using LC-MS, and the in silico analysis will be done with the following software: Human Protein Reference Database, Reactome, Metascape, Sting and David bioinformatic database.