Neuroprotective and behavioral effects of the PPAR³ agonist pioglitazone in a neurodevelopmental model of schizophrenia

• Grant number: 18/20433-2
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: April 01, 2019
• End date: March 31, 2023
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Leonardo Resstel Barbosa Moraes
• Grantee: Andreza Buzolin Sonego
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 17/24304-0 - New perspectives in the use of drugs that modify atypical neurotransmitters in the treatment of neuropsychiatric disorders, AP.TEM
• Associated scholarship(s): 21/06775-0 - Behavioral and electrophysiological effects of PPAR gamma agonist pioglitazone in two-hit model of schizophrenia, BE.EP.PD

Abstract

Schizophrenia is a complex and disabling psychiatric disorder that affects about 1% of the population worldwide. The symptoms can be divided into positive, negative and cognitive ones. The etiology and pathophysiology of schizophrenia, however, are not completely understood, since this disorder has a multifactorial character wtih genetic and environmental factors influencing its development. Among the environmental factors, infection during the pregnancy has been implicated as a risk factor for schizophrenia. However, more than the type of pathogen itself, the maternal immune response generated by the infection seems to be implicated in the development of this disorder in the offspring. Accordingly, a model of schizophrenia based on maternal immune activation (MIA). It consists of the exposure to an immunogenic stimulus, such as viral or bacterial mimetics, during the pregnancy and the assesssment of behavioral and molecular changes in the offspring. Thus, using this model, it has been possible to evaluate the effects of drugas with therapeutic potential for schizophrenia. Since drugs with an anti-inflammatory profile may improve this disorder, a therapeutic alternative could be agonists of peroxisome proliferator-activated receptor gamma (PPAR³). This PPAR isoform is involved in the regulation of metabolic pathways, but also it has an anti-inflammatory profile. The PPAR³ receptors can be found in the central nervous system and their levels are reduced in patients with schizophrenia. In addition, some atypical antipsychotics may increase the expression of these receptors. Therefore, the hypothesis of this study is that the PPAR³ receptor agonist pioglitazone could attenuate neuroimmune and plastic responses, as well as the schizophrenia-like behaviors in the adult offspring of animals submitted to the MIA model.