NEUROPROTECTIVE EFFECTS OF ESSENTIAL FATTY ACIDS FROM LOW-COMMERCIAL-VALUE FISH IN A NEONATAL HYPOXIA MODEL USING SWISS MICE

Omega-3 polyunsaturated fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), play essential roles in neuronal membrane formation and the modulation of neuroinflammation and oxidative stress, especially associated with neonatal hypoxia. However, the high cost of traditional dietary sources limits their consumption. This study aimed to identify low-commercial-value fish species with potential as sources of omega-3 fatty acids and to evaluate their neuroprotective, histopathological, and behavioral effects in Swiss mice subjected to neonatal hypoxia (hermetically sealed chamber with 99.9% nitrogen). Fish species marketed at the Municipal Fish Market of Macaé, Rio de Janeiro, Brazil, were selected, and fatty acid profiles were determined by gas chromatography. Dolphinfish (Coryphaena hippurus) and red seabream (Pagrus major) were selected for the experimental diets based on their favorable lipid profiles and potential as affordable sources of omega-3.Swiss mice were allocated into six experimental groups (n = 8): GC (control - casein-based diet); GCH (hypoxia control - casein-based diet + hypoxia), GDC (dolphinfish control - casein-based diet with freeze-dried dolphinfish), GDH (hypoxia dolphinfish - casein-based diet with freeze-dried dolphinfish + hypoxia), GPC (red seabream control - casein-based diet with freeze-dried seabream) and GPH (hypoxia red seabream - casein-based diet with freeze-dried seabream+hypoxia). The diets were prepared according to the AIN-93G formulation, incorporating 30 g/100 g of freeze-dried fish to provide the protein content. Animals were monitored for 60 days regarding food intake, body weight gain, and behavioral performance in the Elevated Plus Maze test. At the end of the experimental period, the animals were euthanized for histopathological evaluation of nervous tissue and determination of the brain fatty acid profile by lipid extraction, saponification, and fatty acid methylation followed by gas chromatography to determine EPA and DHA concentrations. Red seabream exhibited higher concentrations of DHA (0.13%) and total omega-3 fatty acids (0.14%) than dolphinfish (0.09% for both parameters). The experimental diets presented similar overall compositions, differing primarily by the inclusion of fish. The GPH group showed the highest food intake, whereas no significant differences were observed in body weight gain or relative brain weight among the experimental groups. Behavioral assessment using factor analysis and two-way ANOVA revealed significant differences in latency time, time spent in the maze arms, distance traveled, head-dipping events, freezing episodes, stretch-attend postures, and rearing behavior, indicating that both diet and hypoxia influenced exploratory and anxiety-like behaviors. Dietary supplementation modified the brain lipid profile, increasing EPA concentrations by 300% and DHA levels by 132%, particularly in the GP compared with the GC, while also promoting better preservation of neuronal morphology. Overall, the findings demonstrate that low-commercial-value fish represent affordable natural sources of omega-3 fatty acids with potential neuroprotective properties and may contribute to mitigating the functional consequences of early neurological injury.