Investigation of neuroinflammation markers in MAM rats treated with the antioxidant N-Acetyl-L-Cysteine

• Grant number: 18/22079-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2019
• End date: January 31, 2020
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Cristiane Otero Reis Salum
• Grantee: Thiago Takechi Ohno Bezerra
• Host Institution: Centro de Matemática, Computação e Cognição (CMCC). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

The causes of schizophrenia remain unknown. Some well-established facts are the dopaminergic hyperfunction and the hypofunction of the glutamatergic system in specific regions. One evidence of neurochemical modifications is the loss of the expression of GABAergic paraybumin positive (PV +) interneurons. In addition, the reduction of glutathione (GSH)is verified in postmortem analyzes of schizophrenic patients brains, raising the relation of the oxidative processes with the disorder. In this sense, several studies indicate improvements in some symptoms of schizophrenia when using the GSH precursor, N-acetyl-L-cysteine (NAC), as adjunctive treatment. GSH synthesis occurs primarily in astrocytes that can be identified through expression of the glial fibrillary acidic protein (GFAP). Since astrocytes play a key role in the synaptic metabolism of various neurotransmitters, its dysfunction has been associated with immunological and inflammatory factors in schizophrenia. Several animal models for the study of schizophrenia show increased expression of GFAP in different brain areas and activation of microglia, observed through the expression of bound ionized calcium adapter protein 1 (Iba-1). The model based on the neurodevelopmental disorder through the administration of methylazoxymethanol acetate (MAM) in rats on the 17th day of gestation has been widely used for the study of schizophrenia, since it induces several changes similar to those observed in this disease. However, the expressions of GFAP and IBA1 have not yet been verified in it. A recent study of our group found that the administration of the antioxidant NAC in the animals of this model was able to reverse the observed behavioral deficits. This project intends to investigate in the hippocampus of animals of the MAM model: 1) whether the chronic treatment with NAC also reverses the observed changes in the expression of parvalbumin; 2) if MAM changes the expression of astrocyte, GFAP, and glial IBA1 markers and if NAC treatment is able to reverse these changes.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

LOPES-ROCHA, ANA; BEZERRA, THIAGO OHNO; ZANOTTO, ROBERTA; LAGES NASCIMENTO, INDA; RODRIGUES, ANGELA; SALUM, CRISTIANE. The Antioxidant N-Acetyl-L-Cysteine Restores the Behavioral Deficits in a Neurodevelopmental Model of Schizophrenia Through a Mechanism That Involves Nitric Oxide. FRONTIERS IN PHARMACOLOGY, v. 13, p. 15-pg., 2022-07-12. (11/09548-3, 18/22142-5, 18/22079-1)