BOOSTING THE AGING BRAIN: COMBINED EFFECTS OF INTRAMUSCULAR IGF-1 AND OMEGA-3 FATTY ACIDS ON COGNITION AND ANXIETY

Insulin-like growth factor 1 (IGF-1) is a pleiotropic hormone essential for neuroprotection, synaptic plasticity, and metabolic homeostasis; its age-related decline is linked to cognitive decline and mood disturbances. Omega-3 fatty acids (EPA and DHA) also exert neuroprotective effects via lipid mediators regulating immune and inflammatory responses. Despite their individual benefits, the potential synergy of IGF-1 gene therapy with dietary Omega-3 remains unexplored, particularly regarding sex differences in middle age. Twelve-month-old male and female Sprague Dawley rats received intramuscular injections of an adenoviral vector encoding IGF-1 cDNA (RAd-IGF1) or vehicle, with or without daily oral Omega-3 for 6 months. We assessed treatment interplay across behavioral and molecular domains using marble burying, novel object recognition, Barnes maze, and forced swim tests, and collected brain tissue to study microglial reactivity as a mechanism. IGF-1 treatment modulated recognition memory and spatial learning, reduced anxiety-like behaviors, and mitigated behavioral despair, with distinct patterns between sexes. We are analyzing whether Omega-3 co-administration potentiates these effects via the neuroinflammatory environment, correlating behavioral gains with microglial phenotype shifts. These findings highlight sex-dependent benefits of peripheral IGF-1 gene delivery and support combined nutritional strategies against age-related cognitive and affective impairments.