Balanced polyunsaturated fatty acids diet prevents the D-galactose-induced neuroinflammation and cognitive impairments

The rapid increase of the population aged 65 and over is associated with a higher prevalence of people suffering from cognitive functions alterations. Those impairments are partly due to environmental risk factors such as nutrition. In this context, nutrition, and more specifically the ratio of n-6/n-3 polyunsaturated fatty acids (n-6/n-3 PUFAs), has been extensively studied in relation to cognitive impairment and showed a potential beneficial effect on cognitive decline during aging. Clinical epidemiological studies showed a positive association between the n-3 PUFA consumption and cognitive abilities during aging. Preclinical studies have also demonstrated that dietary n-3 PUFA deficiency disrupts spatial memory, and induces alterations in neuronal functions and increased neuroinflammation, whereas dietary n-3 PUFA supplementation had beneficial effects on cognitive abilities and neuroinflammation in aged mice. Here we showed that a balanced n-6/n-3 PUFAs precursors diet is sufficient to prevent the induction of accelerated aging characteristics such as contextual memory deficits, the altered emotionality status as well as the increased hippocampal neuroinflammation induced by D-galactose injections in mice, involving the activation of the AGE-RAGE pathway. These results highlight the protective effects of a balanced n-6/n-3 PUFAs precursors on accelerated aging induced inflammatory, cognitive and emotional-like alterations. • D-galactose model of accelerated aging induces neuroinflammation, emotional-like and cognitive alterations. • Balanced n-6/n-3 PUFAs precursors diet prevents D-galactose-induced alterations. • Long chain polyunsaturated fatty acids precursors could be used to prevent age-associated central alterations