Investigation of the expression of GFAP, Iba-1 and parvalbumin markers in the prefrontal cortex of MAM rats

• Grant number: 18/22142-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): February 01, 2019
• Effective date (End): January 31, 2020
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Cristiane Otero Reis Salum
• Grantee: Ana Caroline Lopes Rocha
• Host Institution: Centro de Matemática, Computação e Cognição (CMCC). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

Schizophrenia has still unknown causes, although they may be related to dopaminergic hyperfunction and glutamatergic hypofunction, in addition to a possible link with neuroinflammation. Despite its imprecise origin, there are hypotheses about neurodevelopmental disorder leading to animal models based on interventions during this phase. One of these models is the treatment with methylazoxymethanol acetate (MAM), which consists of the injection of this neurotoxin on the 17th day of gestation of Wistar rats, causing damage to the neurodevelopment of the offspring. In their adult phase, these animals present behavioral deficits and neurochemical alterations that resemble some schizophrenia symptoms, including the loss of parvalbumin positive (PV +) interneurons. In recent studies in our laboratory, the antioxidant N-acetyl-L-cysteine (NAC) was able to reverse behavioral deficits caused by the MAM model. In addition, sub-chronic treatment with the nitric oxide precursor, 1-arginine, reversed the beneficial effects of NAC. Thus, the present study intends to investigate: i) the expression of glial markers (GFAP-astrocytes and Iba-1 microglia) and PV + in the pre-frontal cortex of MAM rats treated with NAC or saline for 15 days. It is intended to test both the inflammatory hypothesis in the MAM model and the efficacy of the NAC treatment in reversing the dysfunctions caused in this model. If alterations caused by NAC are detected, it will be investigated whether subchronic treatment with L-arginine (5 days) reverses such changes, according to the behavioral results observed.

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)