Long term adequate n-3 polyunsaturated fatty acid diet protects from depressive-like behavior but not from working memory disruption and brain cytokine expression in aged mice

Abstract

Converging epidemiological studies suggest that dietary essential n-3 polyunsaturated fatty acid (PUFA) are likely to be involved in the pathogenesis of mood and cognitive disorders linked to aging. The question arises as to whether the decreased prevalence of these symptoms in the elderly with high n-3 PUFA consumption is also associated with improved central inflammation, i.e. cytokine activation, in the brain. To answer this, we measured memory performance and emotional behavior as well as cytokine synthesis and PUFA level in the spleen and the cortex of adult and aged mice submitted to a diet with an adequate supply of n-3 PUFA in form of α-linolenic acid (α-LNA) or a n-3 deficient diet. Our results show that docosahexaenoic acid (DHA), the main n-3 PUFA in the brain, was higher in the spleen and cortex of n-3 adequate mice relative to n-3 deficient mice and this difference was maintained throughout life. Interestingly, high level of brain DHA was associated with a decrease in depressive-like symptoms throughout aging. On the opposite, spatial memory was maintained in adult but not in aged n-3 adequate mice relative to n-3 deficient mice. Furthermore, increased interleukin-6 (IL-6) and decreased IL-10 expression were found in the cortex of aged mice independently of the diets. All together, our results suggest that n-3 PUFA dietary supply in the form of α-LNA is sufficient to protect from deficits in emotional behavior but not from memory disruption and brain proinflammatory cytokine expression linked to age.