Docosahexaenoic acid supplementation of primary rat hippocampal neurons attenuates the neurotoxicity induced by aggregated amyloid beta protein(42) and up-regulates cytoskeletal protein expression.
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.
Department of Physiology, National Taiwan University College of Medicine, Taipei 100, Taiwan.
Pao-Yuan
PY
Wang
Jen-Jui
JJ
Chen
Hui-Min
HM
Su
D000107:Acetylation; D000544:Alzheimer Disease / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004281:Docosahexaenoic Acids / Q000008:administration & dosage* / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000378:metabolism; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014404:Tubulin / Q000378:metabolism; D015854:Up-Regulation
D016229:Amyloid beta-Peptides; D003598:Cytoskeletal Proteins; D005227:Fatty Acids; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D014404:Tubulin; C075222:amyloid beta-protein (1-42); C039520:tyrosine-tubulin; D004281:Docosahexaenoic Acids