Influência do sexo e efeito preventivo dos ácidos graxos poli-insaturados ômega-3 sobre alterações comportamentais e neuro-oxidativas em animais submetidos ao modelo de esquizofrenia por desafio imune neonatal combinado a estresse na adolescência

• Autor(a) principal: Costa, Ayane Edwiges Moura da
• Data de Publicação: 2018
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da Universidade Federal do Ceará (UFC)
• Texto Completo: http://www.repositorio.ufc.br/handle/riufc/31429
• topic: Esquizofrenia; Ácidos graxos ômega-3; Estresse Oxidativo

Schizophrenia is a neurodevelopmental disorder triggered by environmental factors, such as viral infections in early stages of life. In this context, an animal model induced by neonatal immune activation has gained evidence in recent years, with the Polyinosinic-polycytidylic acid mime virus (Poly(I:C)) as a first challenge, contributing to the vulnerability of offspring to the development of neuroimmune and behavioral abnormalities associated with stress in the puberty as a second challenge. Studies indicate that by attenuating inflammatory reactions caused by stress in adolescence, it is possible to prevent schizophrenia. It is known that omega-3, a long-chain polyunsaturated fatty acid, can reduce symptoms of schizophrenia and is a good strategy in preventing psychosis in individuals at high risk for the disorder. Based on the neuroprotective properties of omega-3, the present study evaluated the effects of this fatty acid and the influence of sex on behavioral and oxidative changes in animals submitted to the schizophrenia model induced by neonatal immune challenge, combined with adolescence stress. Swiss mice, male and female, were divided into 4 groups after birth. Poly(I:C) was administered in postnatal days (PND) 5, 6 and 7 once a day (2 mg/Kg, i.p.). From PND35 to PND43, the animals were submitted to unpredictable stress events. Administration of n-3 polyunsaturated fatty acids occurred from PND30 to PND60. Pre-pulse inhibition (PPI), social interaction, and Y maze tests, conducted between PND70 and PND72, evaluated the behavioral changes associated to the positive, negative and cognitive symptoms of schizophrenia, respectively. Reduced glutathione (GSH), nitrite and thiobarbituric acid reactive substances (TBARS) were investigated in brain areas and in the blood of the animals as adults in the search for neurobiological alterations of schizophrenia. Statistical analyzes were performed by two-way ANOVA, followed by the Tukey test. Significance level was defined as P ≤ 0.05. The results showed that male and female mice, submitted to both challenges, presented considerable deficits in IPP, social interaction and working memory. Omega-3 prevented these deficits in both sexes. Regarding the parameters of oxidative stress, the female saline group presented high levels of GSH, in comparison to male. Females submitted to both challenges exhibited reduced levels of GSH. Regarding nitrite levels, it was verified that omega-3 prevented, in females submitted to the two-hit model, the increase of nitrite levels in the prefrontal cortex (CPF), hippocampus (HC) and striatum (ST). Males submitted to neonatal immune challenge, combined with stress in adolescence, presented high levels of plasma nitrite in comparison to the saline group. Omega-3 significantly prevented the increase of TBARS levels in CPF, HC and EC of males submitted to the two-hit model. It was also observed that omega-3 prevented, in females submitted to both challenges, the increase of plasma TBARS levels. The results suggest that this polyunsaturated fatty acid is therefore an accessible and effective alternative in the prevention of behavioral and oxidative alterations related to schizophrenia.