Banca de QUALIFICAÇÃO: LUIS FELIPE RAMOS TOSCANO

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
STUDENT : LUIS FELIPE RAMOS TOSCANO
DATE: 18/07/2023
TIME: 14:00
LOCAL: on-line
TITLE:

EVALUATION OF CYTOKINES IN THE BLOOD AND BRAIN OF MAM MODEL RATS TREATED WITH THE ANTIOXIDANT N-ACETYL-CYSTEINE IN THE PUBERAL PHASE

PAGES: 68
BIG AREA: Ciências Biológicas
AREA: Farmacologia
SUBÁREA: Neuropsicofarmacologia
SUMMARY:

The cause of schizophrenia is still widely studied, several studies have found changes in dopaminergic and glutamatergic neurotransmission, as well as a reduction in inhibitory parvalbumina-positive interneurons (PVI) in the prefrontal cortex (CPF) and ventral hippocampus. This process is related to oxidative stress and increased neuroinflammation, observed through elevated levels of pro-inflammatory cytokines, and decreased levels of anti-inflammatory cytokines. The antioxidant N-acetyl-L-cysteine (NAC) was tested in several animal models of schizophrenia and was able to prevent the loss of PVI in the ventral hippocampus, in addition to decreasing behavioral changes in many studies. The animal model of schizophrenia based on the interruption of neurodevelopment through the administration of methylazoxymethanol acetate (MAM) in rats on the 17th gestational day induces behavioral, neuronal and physiological alterations consistent with what is observed in other models of schizophrenia, as well as in humans. Treatment of MAM model animals with NAC has shown promising results, reducing several behavioral deficits caused by MAM and aiding in the general understanding of the pathophysiology of this disease. However, not all the mechanisms by which NAC acts in the MAM model have been clearly described, and data analyzing its influence on the levels of pro- and anti-inflammatory cytokines is scarce. This project aims to evaluate whether there are neuroinflammatory changes in male and female rats of the MAM model, on acute or chronic treatment or not with NAC in the pubertal phase, investigating the levels of pro-inflammatory cytokines IFN-γ, IL-1β, IL-6 , IL-2 and TNF-α, and anti-inflammatory IL-4 and IL-10 in peripheral blood, CPF and hippocampus, relating these results to behavioral changes. The experiment began with the identification of the estrous cycle phase of the rats and the coupling during the fertile period, being considered pregnant with the identification of sperm in the vaginal smear. On gestational day (GD) 17, pregnant rats were treated, with 25 mg/kg (1mg/ml) of MAM or saline. After birth and weaning (PN21) the male pups were separated from the females. When the animals completed between 43-45 days of life, i.p. treatment was started with saline or NAC 250 mg/kg. 1h after this first application, the Acute Experiment was performed, in which the animals were submitted to the Pre-Pulse Inhibition Test (PPI), Locomotion Test in the Arena and Social Interaction Test (SI). The animals were chronically treated for 15 days. 24 hours after the last dose of NAC or saline, the Chronic Experiment was performed, with the same behavioral experiments as in the Acute Experiment and peripheral blood and brain tissue were collected for subsequent analysis of cytokines. In the Acute Experiment, male MAM treated rats showed a higher total distance traveled in the Locomotion Test and a decrease in time spent on active interaction in the IS, compared to the saline group. NAC treated rats showed a higher mean distance in the IS when compared to the saline group. Females MAM treated rats showed a decrease in the time spent in active interaction and an increase frequency of self-cleaning in the IS when compared to the saline group. In the Chronic Experiment, the males MAM treated rats showed a decrease in time spent on active interaction and a longer time spent in the self-grooming behavior in the IS, when compared to the saline group. A general effect of NAC in increasing PPI was also observed. The females MAM treated rats, on the other hand, presented a higher average distance, while the NAC treated rats presented a lower average distance in the IS, when compared to the saline group. The presented results suggest that the acute or chronic NAC treatment in the pubertal phase, in an way, produces some effects reducing the behavioral deficits in the MAM model in males, as in the time of active interaction in the IS test. In females this should be investigated by evaluating the phase of the estrous cycle.

COMMITTEE MEMBERS:
Presidente - Interno ao Programa - 1994696 - SILVIA HONDA TAKADA
Membro Titular - Examinador(a) Externo à Instituição - ANA CAROLINA ISSY - USP
Membro Titular - Examinador(a) Externo à Instituição - VANESSA COSTHEK ABÍLIO - UNIFESP
Membro Suplente - Examinador(a) Interno ao Programa - 1893240 - RAQUEL VECCHIO FORNARI