Targeting Oxidative Stress in Brain Aging. Effects of Increasing DHA Intake

Abstract

In the aging brain or in neurodegenerative disorders, the pronounced depletion of DHA-enriched phospholipids may indicate a persistent oxidative catabolic degradation, unmatched by a proper reacylation of the PUFAs. Brain tissue is particularly vulnerable to oxidative damage, because of the high consumption of oxygen, the easily peroxidizable high content of PUFAs in neuronal membranes, the low rate of cell turnover, and the high production of reactive oxygen and nitrogen species. Additionally, it is less endowed with a robust and diverse enzymatic and nonenzymatic antioxidant arsenal. In previous research, we have demonstrated a positive effect of fish oils on oxidative stress and inflammation associated to high caloric intake in animal models. The effect was largely dependent on the EPA/DHA ratios and closely related with an activation of the endogenous antioxidant system. As a consequence, lipids and proteins of plasma and target organs and tissues resulted specifically protected. On these basis, the present work aims to study the effect of increasing intake of DHA on the modulation of the lipid composition of brain cortex and the oxidative stress occurring in adult rats. Cerebral cortex plays a key role in memory, attention, perception, cognition and serve a wide range of neurologic functions. For that, an animal model of adult Wistar rats fed with standard diets supplemented with increasing DHA levels was used. Epilipidomics and lipidomics were applied to brain cortex and results were correlated with the endogenous antioxidant system. Results evidenced a modification of the lipid class pattern highly dependent of the PUFA intake. Interestingly, phrenosin (α-hydroxy GalCer) and phosphatidylethanolamine were found decreased while the levels of phosphatidylcholine were significantly increased. Supplementation with fish oils resulted in an enhancement of more than 2% of DHA in cortex lipids. The study of the specific oxidation products reveals a significant protection of cortex lipids in animals fed a high percent of DHA. It was noteworthy the specific protection found in oxidised phospholipids as phosphatidylcholine. Results were correlated with the enzymatic antioxidant content and the systemic level of oxidative stress detected in plasma and other tissues. To sum up, the regulation of lipid composition and oxidative stress in brain cortex associated to increasing DHA intake appears to have a pivotal role in both the healthy brain aging and the design of targeted-strategies.