Background: Supplementation of omega-3 fatty acids has shown efficacy to prevent conversion to schizophrenia in ultra-high risk population. In this study we evaluated the efficacy of omega-3 in preventing ketamine-induced effects in an animal model of schizophrenia and its effect on BDNF serum levels. Methods: Forty-eight Wistar male rats were included. Twenty-four received 0.8g/kg omega-3 and 24 tween, both groups at the 30Th day of life for 15 days. Each group was split in two 12-animals groups to receive along the following 7 days 25 mg/kg of ketamine or saline intra-peritoneal. The total treatment period was 22 days. Locomotor and exploratory activity (open-field task), memory test (inhibitory avoidance test) and social interaction between pairs (latency time to first contact, number and time of contacts) were evaluated at the 52nd day of life. Bloods for BDNF were withdrawal at the 53rd day of life. Results: Social interactions were decreased in time and number of contacts, and latency time to first contact was increased in ketamine group. Ketamine increased covered distances in 5, 10 and 15 minutes. Ketamine+omega-3 were not different than controls and omega-3 alone in 10 and 15 minutes. On the inhibitory avoidance memory test, omega-3 has prevented ketamine-induced impairment on working, short and late memories. BDNF levels were higher in ketamine+omega-3 group (p=0.009). Conclusions: Omega-3, in a ketamine-induced model of schizophrenia, prevents in adolescents Wistar male rats the equivalent in humans of positive, negative and, cognitive symptoms of schizophrenia. Moreover it increases BDNF in prevention treatment of ketamine effects.

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Although folic acid (FA) supplementation is known to influence numerous physiological functions, especially during pregnancy, little is known about its direct effects on the mothers' health. However, this vitamin is essential for the health of the mother and for the normal growth and development of the fetus. Thus, the aim of this study was (1) to evaluate the cognitive effects and biochemical markers produced by the AIN-93 diet (control), the AIN-93 diet supplemented with different doses of FA (5, 10, and 50 mg/kg), and a FA-deficient diet during pregnancy and lactation in female mother rats (dams) and (2) to evaluate the effect of maternal diets on inflammatory parameters in the adult offspring which were subjected to an animal model of schizophrenia (SZ) induced by ketamine (Ket). Our study demonstrated through the Y-maze test that rats subjected to the FA-deficient diet showed significant deficits in spatial memory, while animals supplemented with FA (5 and 10 mg/kg) showed no deficit in spatial memory. Our results also suggest that the rats subjected to the FA-deficient diet had increased levels of carbonylated proteins in the frontal cortex and hippocampus and also increased plasma levels of homocysteine (Hcy). Folate was able to prevent cognitive impairments in the rats supplemented with FA (5 and 10 mg/kg), data which may be attributed to the antioxidant effect of the vitamin. Moreover, FA prevented protein damage and elevations in Hcy levels in the rats subjected to different doses of this vitamin (5, 10, and 50 mg/kg). We verified a significant increase of the anti-inflammatory cytokine (interleukin-4 (IL-4)) and a reduction in the plasma levels of proinflammatory cytokines (interleukin-6 (IL-6)) and TNF-α) in the dams that were subjected to the diets supplemented with FA (5, 10, and 50 mg/kg), showing the possible anti-inflammatory effects of FA during pregnancy and lactation. In general, we also found that in the adult offspring that were subjected to an animal model of SZ, FA had a protective effect in relation to the levels of IL-4, IL-6, and TNF-α, which indicates that the action of FA persisted in the adult offspring, since FA showed a lasting effect on the inflammatory response, which was similar in both the dams and their offspring. In conclusion, the importance of supplementation with FA during pregnancy and lactation should be emphasized, not only for the benefit of the offspring but also for the health of the mother. All this is due to the considerable protective effect of this vitamin against oxidative damage, cognitive impairment, hyperhomocysteinemia, immune function, and also its ability in preventing common processes in post-pregnancy stages, as well as in reducing the risks of neurodevelopmental disorders and enhancing fetal immune development.

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New studies suggest that polyunsaturated fatty acids, such as omega-3, may reduce the symptoms of schizophrenia. The present study evaluated the preventive effect of omega-3 on interleukines (IL) and neurotrophin brain-derived neurotrophic factor (BDNF) levels in the brains of young rats subjected to a model of schizophrenia. Treatment was performed over 21 days, starting on the 30th day of rat's life. After 14 days of treatment with omega-3 or vehicle, a concomitant treatment with saline or ketamine (25 mg/kg) was started and maintained until the last day of the experiment. BDNF levels in the rat's prefrontal cortex were decreased at 1 h and 24 h after the last administration of ketamine, whereas the group administered with ketamine and omega-3 showed a decrease in BDNF levels only after 24 h. In contrast, both interventions induced similar responses in levels of IL-1β and IL6. These findings suggest that the similarity of IL-1β and IL6 levels in our experimental groups is due to the mechanism of action of ketamine on the immune system. More studies have to be carried out to explain this pathology. In conclusion, according to previous studies and considering the current study, we could suggest a prophylactic role of omega-3 against the outcome of symptoms associated with schizophrenia.