Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by extracellular deposits of fibrillar aggregates of amyloid-β peptide (Aβ). 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 Aβ-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 μM DHA for 8 days, then were treated with 5 μM aggregated Aβ42 for 1 day. We found that supplementation with 5–10 μM 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 μM DHA attenuated aggregated Aβ42-induced neurotoxicity and protected hippocampal neurons, with 25 μM 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 Aβ and in maintaining hippocampal neuron survival.
Pao-Yuan Wang, Jen-Jui Chen, Hui-Min Su. Docosahexaenoic acid supplementation of primary rat hippocampal neurons attenuates the neurotoxicity induced by aggregated amyloid beta protein42 and up-regulates cytoskeletal protein expression. Journal of Nutritional Biochemistry 2010 April Department of Physiology, National Taiwan University College of Medicine, Taipei 100, Taiwan.