Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by extracellular deposits of fibrillar aggregates of amyloid-beta peptide (Abeta). Levels of docosahexaenoic acid (DHA, 22:6n-3), the major fatty acid component of the neuronal membrane, are reduced in the AD hippocampus. We hypothesized that hippocampal neurons with reduced DHA levels would be more susceptible to aggregated Abeta-induced death and that this might be overcome by increasing hippocampal neuronal DHA levels. Embryonic Day 18 rat hippocampal cells were cultured in neurobasal medium with B27 supplemented with 0-100 microM DHA for 8 days, then were treated with 5 microM aggregated Abeta(42) for 1 day. We found that supplementation with 5-10 microM DHA, which resulted in hippocampal neuron DHA levels of 12-16% of total fatty acids, was optimal for primary hippocampal neuronal survival, whereas supplementation with 5 or 25 microM DHA attenuated aggregated Abeta(42)-induced neurotoxicity and protected hippocampal neurons, with 25 microM DHA being more effective. DHA supplementation also resulted in significant up-regulation of expression of tyrosine tubulin and acetylated tubulin. We suggest that hippocampal neuronal DHA levels may be critical for AD prevention by attenuating the neurotoxicity induced by Abeta and in maintaining hippocampal neuron survival.
Copyright 2010 Elsevier Inc. All rights reserved.