Combination of estrogen and dietary DHA are required for hippocampal lipid homeostasis. Relevance for Alzheimer’s disease therapeutics

Resumen

Diet has emerged as highly important for brain preservation. Increasing epidemiological studies have indicated a relationship between lipid diet and preservation of neuronal functioning. In particular, learning and memory functions take place in the hippocampus, a brain area that seems to be high sensitive to lipid fluctuations. In this sense, current evidences have demonstrated that hippocampal homeostasis is regulated by genetic, dietary and hormonal factors. Indeed, alterations in these factors have been associated withAlzheimer’s disease (AD). However, theorchestration of these parameters in correlation to neurodegenerative processes remains largely unknown. In an attempt to explore the combined effects of estrogen status, dietary doses of docosahexaenoic acid (DHA), and genotype (wild-type or transgenic APP/PS1 mice as a model of AD) in the hippocampus, we have performed multifactorial analyses. Our results have demonstrated that the three factors strongly cross-interact, and affect lipid matrix. The most significant alterations in lipid profiles were observed in APP/PS1 deprived of estrogens and exposed to a low-DHA diet. Interestingly, those animals receiving estrogen and a high-DHA diet showed a hippocampal lipid profile similar to control animals. Furthermore, proteins involved in lipid biosynthesis machinery exhibited altered patterns of gene expression, thus correlating with the variations in the combined experimental factors. Overall, these data demonstrate that hippocampal lipid homeostasis is strongly affected by the combination of, both, sex hormone and DHA diet conditions. These observations may pave the way of new approaches for AD therapeutics