Investigation of GFAP, parvalbumin and nNOS expressions in the MAM model after N-acetyl-L-cysteine treatment during prepubertal phase

• Grant number: 20/11179-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2021
• End date: March 31, 2022
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Cristiane Otero Reis Salum
• Grantee: Roberta Benedetti Zanotto
• Host Institution: Centro de Matemática, Computação e Cognição (CMCC). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

Schizophrenia is a psychiatric disorder whose sources are still unknown and has got a range of associated symptoms. The onset of this disease is considered when the first psychotic episode appears, which usually occurs between the late adolescence and early adulthood. There are several hypotheses regarding the development of schizophrenia, including neurodevelopment, which neurobiological and behavioral changes can be triggered by an interaction of genetic and environmental factors. Schizophrenic patients presents several neurochemical alterations, such as decreased expression of positive parvalbumin interneurons (PV+), changes in the number of astrocytes expressing glial fibrillary acidic protein (GFAP), reduced antioxidant glutathione (GSH) and increased levels of nitric oxide (NO) due to the excessive formation of reactive oxygen species (ROS), an indicative of oxidative stress. In the central nervous system, NO is produced by the amino acid L-arginine, catalyzed by the enzyme nNOS. Currently, schizophrenia treatment is based on antipsychotics, that have adverse side effects and low efficacy on negative and cognitive symptoms. N-acetyl-L-cysteine is an antioxidant acting as a precursor to GSH. NAC administration in MAM rats has been considered effective in reducing behavioral deficits caused by the mitotoxin. Data on the effects of NAC treatment in stages that precede the onset of the disease, the prodromal phase, are still unknown. Thus, the present study intends to investigate the effects of chronic NAC treatment in MAM rats during the prepubertal phase, throughout the expression of GFAP, PV and nNOS markers.