N-3 PUFA supplementation in adulthood modulates diet-induced depressive-like phenotype in female rats

Low consumption of omega-3 polyunsaturated fatty acids (n-3 PUFA) during development has been linked to increased risk of developing depressive symptoms. The present study assesses the influence of chronic n-3 PUFA supplementation in a rodent model of depressive-like phenotype induced by long-life depletion of n-3 PUFA in the diet. These behavioural and biological consequences already start to become apparent in adolescence and tend to worsen if the n-3 PUFA deficiency is prolonged. Here, we investigated whether the reintroduction of n-3 PUFA at a later stage of development can reverse these alterations. Thus, female Wistar rats, subjected to a diet low in n-3 PUFA since fetal stage, were re-exposed to n-3 PUFA from week 8 of life until week 16. N-3 PUFA enriched diet improved these behavioural and neurochemical deficits by restoring neurotransmitter levels. Levels of nerve growth factor in prefrontal cortex (PFC), brain-derived neurotrophic factor and synaptophysin in PFC and hippocampus were significantly enhanced, suggesting that the n-3 PUFA supplementation promotes synaptic plasticity. However, Amyloid oligomers and Amyloid-beta precursor protein levels were only partially recovered, while improving calmodulin-dependent protein kinase II levels in PFC. Finally, n-3 PUFA replenishment reduced plasma levels of 3-hydroxykynurenine, a pro-oxidant metabolite of the tryptophan/kynurenine pathway, but could not restore serotonin amount nor kynurenine/tryptophan ratio. In conclusion, our data support the hypothesis that the reintroduction of n-3 PUFA at a late phase of development can provide significant benefits to the CNS, although some long-term neurotoxic effects may not be fully reversible.