Efeito da suplementação de ômega-3 em um modelo animal de esquizofrenia induzido por cetamina

Abstract

The estimated new cancer cases worldwide in 2007 were 12 million, with 5.4 million cases diagnosed in developed and 6.7 millions in developing countries. The number of cancer-related deaths was 7.6 million, 2.9 million in developed and 4.7 million in developing countries. Malignant neoplasm ranks second (12.5%) as causes of death worldwide, surpassed by cardiovascular causes (19.6%). Gastric Cancer (GC) ranks fourth as the most frequent cause of cancer worldwide, with one million new cases in 2007, behind lung, breast and colon and rectum. 70% of new cases occur in developing countries. Currently, GC is the second most common cause of cancer deaths, accounting for 800,000 deaths annually. In Brazil, estimates for 2010 point to the occurrence of 489,270 new cases of cancer, and the GC occupying fifth place in attendance with 21,500 new cases. The acquisition of the migratory behavior of cancer cells is a prerequisite to break up organized tissue structures, invade and metastasize. Recently, the expression of proteins that block actin has been associated with the invasive behavior of tumors. The Cofilin is an actin-blocking protein, which regulates the actin cytoskeleton to maintain and depolymerize actin filaments. The interest for cofilin and its cascade have increased because of its relationship with tumor invasion, metastasis and be a potential prognostic factor in cancer. We conducted a retrospective study, observational, descriptive and analytical. We used all the pathological reports of patients undergoing gastrectomy for adenocarcinoma between June 2002 and June 2009, totaling 130 cases. Of these, 44 cases were selected randomly. The average age of patients was 68 years, with 63.6% of male sex. In assessing the depth of invasion, advanced lesions with involvement beyond the submucosa corresponded with 72.7% of cases. The diffuse type in Lauren's classification was the most prevalent with 68.1%. The bacterium H. pylori was positive in 72.7% of carcinomas. Lymph nodes involvement accounted for 70.4% of cases. At the end of the study 56.8% of patients were alive. When applied statistical tests to assess the relationship of cofilin with the other independent variables, only the depth of tumor invasion and the presence of positive lymph node were statistically significant. In conclusion, despite the cofilin is present in locally advanced tumors and lymph node metastases, and the small number of patients in the sample, we cannot conclude that it can be used as a prognostic factor.

Schizophrenia is considered a neurodevelopmental psychiatric disorder severe that usually affects the individual in the young stage. For this reason, prevention and early diagnosis become a goal to improve the long-term results. The omega 3 fatty acids (ω-3) have demonstrated efficacy for preventing the conversion of schizophrenia in a population of ultra high risk. The present study aimed to evaluate the effect of supplementation of ω-3 through behavioral and biochemical parameters in an animal model of schizophrenia induced by ketamine. The research used 144 male Wistar rats 30 days old that were separated into two groups for administration of ω-3 or vehicle for 15 days. Subsequently, these groups were subdivided into four groups of 12 mice for intervention with ketamine or saline for 7 days. The locomotor activity, social interaction test and memory tests were evaluated at day 52 of life of the animals. The blood was collected minutes before the animals were killed and serum obtained after 24 hours to evaluate the levels of brain-derived neurotrophic factor (BDNF). The animals were sacrificed after the behavioral tests and striatum, prefrontal cortex and hippocampus extracted for mRNA BDNF expression analysis. The results showed, for the times of 5, 10 and 15 minutes, there was an increase in locomotor activity in the ketamine group compared to control. It was observed in group ω-3 plus ketamine that hyperlocomotion caused by ketamine was prevented at 10 and 15 minutes upon administration of ω-3. Regarding the social interaction test, it was found that animals treated with ketamine did not show difference in latency to the start of the test compared to the control group. However, showed less contacts with each other, as well as a lower total time of interaction when compared to the control. The group ω-3 plus ketamine did not show impaired social interaction. This study showed that there was significant impairment of immediate memory, short and long term in the ketamine treated group compared to control. In group ω-3 plus ketamine, memories immediate, short and long term have been preserved. Serum levels of BDNF were significantly higher in ω-3 plus ketamine group compared to control, ω-3 and ketamine group. The results of the expression mRNA BDNF showed no significant difference among the four groups analyzed in different brain regions. These findings prove that the administration of ω-3 prevents the positive symptoms, negative and cognitive impairment in an animal model of schizophrenia induced by ketamine in the prodromal phase, providing thus, important evidence for future clinical trials in confirming the use of ω-3 to prevent this disorder. It also reinforces the beneficial role of fatty acids in brain protection of individuals at ultra high risk for psychosis.