Enriched and deficient omega-3 PUFA exposure from gestation to adulthood modulates anxiety-related behavior and stress- and neuroplasticity-related brain gene expression in mice.

Omega-3 polyunsaturated fatty acids (PUFAs) are essential for brain development and function, affecting inflammation, neurotransmission, and neuroplasticity. These nutrients are associated with benefits in managing stress, sleep disorders, anxiety, and mild cognitive impairment. This study investigated the effects of chronic exposure to varying omega-3 PUFA levels, from gestation to adulthood, on behavioral and molecular aspects related to memory, anxiety, and depression in male mice. Dams received one of three diets: Control (soybean oil, 7 %), omega-3 Deficient (sunflower oil, 7 %), or omega-3 Enriched (4.2 % cod liver oil +2.8 % soybean oil). After weaning, the offspring continued on their respective diets until adulthood. The omega-3 Deficient diet led to increased locomotor activity, anxiety-like behavior, and a trend toward greater immobility time in the tail suspension test. It also upregulated the expression of Avp and its receptor Avpr1b within the hypothalamic-pituitary axis, suggesting a potential mechanistic link between omega-3 deficiency and mood disorders. In contrast, the Enriched group exhibited reduced locomotor activity and anxiolytic-like behavior in the elevated plus maze. At the molecular level, the Deficient diet downregulated Grin1, while the Enriched diet upregulated Creb1 in the hippocampus, providing insight into how omega-3 PUFAs influence cognitive processes. Chronic insufficient omega-3 consumption throughout development and adulthood may negatively affect anxiety- and depression-related responses, while high omega-3 intake may play a protective role in anxiety regulation. These findings deepen our understanding of the role of omega-3 PUFAs in affective and cognitive regulation, highlighting the significance of balanced intake to support mental health.