Docosahexaenoic acid withstands the Aβ(25-35)-induced neurotoxicity in SH-SY5Y cells.
BACKGROUND
Docosahexaenoic acid (DHA, C22:6, n-3) ameliorates the memory-related learning deficits of Alzheimer's disease (AD), which is characterized by fibrillar amyloid deposits in the affected brains. Here, we have investigated whether DHA-induced inhibition of Amyloid β-peptide(25-35) (Aβ(25-35)) fibrillation limits or deteriorates the toxicity of the human neuroblastoma cells (SH-SY5Y).


METHODS
In vitro fibrillation of Aβ(25-35) was performed in the absence or presence of DHA. Afterwards, SH-SY5Y cells were incubated with Aβ(25-35) in absence or presence 20 μM DHA to evaluate its effect on the Aβ(25-35)-induced neurotoxicity by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)]-redox and TUNEL (TdT-mediated dUTP-biotin nick end-labeling) assay and immunohistochemistry. The level of Aβ(25-35)-induced lipid peroxide (LPO) was determined in the absence or presence of oligomer-specific antibody. Fatty acid profile was estimated by gas chromatography.


RESULTS
DHA significantly reduced the Aβ(25-35) in vitro fibrillation, as indicated by fluorospectroscopy and transmission electron microscopy. Aβ(25-35) decreased the MTT-redox activity and increased the apoptotic damage and levels of LPO when compared with those of the controls. However, when the SH-SY5Y cells were treated with Aβ(25-35) in the presence of DHA, MTT redox potential significantly increased and the levels LPO decreased, suggesting an inhibition of the Aβ(25-35)-induced neurotoxicity. DHA improved the Aβ(25-35) induced DNA damage and axodendritic loss, with a concomitant increase in the cellular level of DHA, suggesting DHA protects the cell from neurotoxic degeneration.


CONCLUSIONS
DHA not only inhibits the in vitro fibrillation but also resists the Aβ(25-35)-induced toxicity in the neuronal cells. This might be the basis of the DHA-induced amelioration of Aβ-induced neurodegeneration and related cognitive deficits.
Hashimoto
Michio
M
Department of Environmental Physiology, Shimane University Faculty of Medicine, Izumo, Shimane 693-8501, Japan. michio1@med.shimane-u.ac.jp
Katakura
Masanori
M
Hossain
Shahdat
S
Rahman
Azizur
A
Shimada
Toshio
T
Shido
Osamu
O
D000544:Alzheimer Disease / Q000517:prevention & control; D000682:Amyloid / Q000378:metabolism* / Q000648:ultrastructure; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000633:toxicity*; D017209:Apoptosis; D001369:Axons / Q000378:metabolism / Q000648:ultrastructure; D002460:Cell Line; D002470:Cell Survival; D004249:DNA Damage; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D020287:In Situ Nick-End Labeling; D008054:Lipid Peroxides / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000378:metabolism* / Q000633:toxicity*
D000682:Amyloid; D016229:Amyloid beta-Peptides; D005227:Fatty Acids; D008054:Lipid Peroxides; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D004281:Docosahexaenoic Acids