Walnuts Modulate Cognition, Inflammation, and BDNF Expression in Rats

Aging is associated with increased neuroinflammation and a decrease in neuroplasticity, contributing to cognitive decline and increased risk for neurodegenerative disease. Nutritional interventions, such as walnut supplementation, may counteract these effects due to walnuts' high content of polyunsaturated fatty acids, polyphenols, and other bioactive compounds. Prior studies suggest walnuts improve cognitive function and modulate neuroplasticity-, inflammatory-, and oxidative stress-associated pathways in both animal models and humans. We investigated the effects of 8 weeks of dietary walnut supplementation (0%, 6%, or 9% w/w) on behavioral and molecular markers of brain aging in young and aged Fischer 344 rats. Cognitive performance was assessed with the radial arm water maze (RAWM). To examine potential anti-inflammatory mechanisms, we treated lipopolysaccharide (LPS)-activated BV-2 microglial cells with serum collected from the rats pre- and post-diet and quantified nitric oxide (NO) release and inducible nitric oxide synthase (iNOS) expression. Additionally, gene expression of brain-derived neurotrophic factor (BDNF) was evaluated in the hippocampus and frontal cortex tissues. Our results demonstrated that walnut supplementation improved performance by decreasing the number of errors made in the RAWM. Serum from walnut-fed rats significantly reduced NO release and iNOS expression in LPS-stimulated microglia. Hippocampal BDNF mRNA expression also differed according to age and diet, with higher expression in aged than young rats receiving the 9% walnut diet. These findings suggest that dietary walnuts may support healthy brain aging through effects on cognitive performance and circulating factors that modulate inflammatory responses and BDNF expression.