Lifelong Nutritional Omega-3 Deficiency Evokes Depressive-Like State Through Soluble Beta Amyloid

Recent evidence pointed out that the prevalence of depression has reached epidemic proportions in last decades. This increase has been linked to many environmental factors, among these the influence of dietary factors has gained great attention. In particular, it has been reported that low n-3 polyunsaturated fatty acid (n-3 PUFA) intake in diet is correlated to the development of depressive and anxiety-like symptoms. Furthermore, maternal malnutrition is a widely accepted risk factor for developing mental illness in later adulthood; among others, depression has been strongly associated to this event. On the other hand, we have previously found that acute intracerebral injection of the soluble beta amyloid 1-42 (A beta(1-42)) peptide induces a depressive-like behavior in rats, associated to altered hypothalamic-pituitary-adrenal (HPA) axis activation and reduced cortical serotonin and neurotrophin levels. The aim of the present work was to study the effect of pre- and post-natal (5 weeks post-weaning) exposure to diets differently enriched in n-3, n-6, as well as n-6/n-3 PUFA balanced, on immobility time displayed on the forced swimming test (FST), along with neuroendocrine quantification in offspring rats. Results showed that n-6 PUFA-enriched diet increased depressive- and anxiety-like behaviors, as shown by the elevation in the immobility time in the FST test and self-grooming in the open field test. Those effects were accompanied by reduced cortical serotonin, high plasmatic corticosterone and hypothalamic corticotropin-releasing factor levels. Finally, enhanced plasmatic A beta(1-42) levels after n-6 PUFA diet and reduced plasmatic A beta(1-42) levels after n-3 PUFA were found. Taken together, our data indicate that A beta(1-42) might be crucially involved in behavioral alterations found after n-6 rich PUFA diet and strongly endorse the protective role of n-3 and the detrimental effect of improper n-6 PUFA diet consumption.