Behavioral and electrophysiological effects of PPAR gamma agonist pioglitazone in two-hit model of schizophrenia

• Grant number: 21/06775-0
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: November 01, 2021
• End date: October 31, 2022
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Leonardo Resstel Barbosa Moraes
• Grantee: Andreza Buzolin Sonego
• Supervisor: Anthony Albert Grace
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: University of Pittsburgh (Pitt), United States
• Associated to the scholarship: 18/20433-2 - Neuroprotective and behavioral effects of the PPAR³ agonist pioglitazone in a neurodevelopmental model of schizophrenia, BP.PD

Abstract

Schizophrenia is a complex psychiatric disorder that affects approximately 1% of the population worldwide, whose symptoms can be divided in positive, negative and cognitive. The etiology and pathophysiology of this disorder, however, are not yet completely understood, with genetic and environmental factors influencing its development. Among the environmental insults, maternal infection and stress exposure, especially during childhood and adolescence, have been implicated as risk factors for schizophrenia. Both insults induce an exacerbated inflammatory response, which could mediate disturbance of neurodevelopmental processes and, ultimately, malfunctioning of neural systems observed in schizophrenia. Thus, anti-inflammatory drugs may potentially be used to treat this disorder. Among them, the agonists of peroxisome proliferator-activated receptor gamma (PPAR³) could be explored as a therapeutic alternative. This isoform of PPAR receptors is involved in the regulation of metabolic pathways, but also presents anti-inflammatory properties. These receptors can be found in the central nervous system and their expression is reduced in patients with schizophrenia. Furthermore, some antipsychotic drugs can increase the expression of PPAR³ receptors. Therefore, the hypothesis of this study is that the PPAR³ agonist pioglitazone would attenuate the behavioral and electrophysiological alterations found in a two-hit model of schizophrenia. (AU)