Docosahexaenoic acid withstands the Aβ25-35-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 beta-peptide(25-35) (A beta(25-35)) fibrillation limits or deteriorates the toxicity of the human neuroblastoma cells (SH-SY5Y). Experimental methods: In vitro fibrillation of A beta(25-35) was performed in the absence or presence of DHA. Afterwards. SH-SY5Y cells were incubated with A beta(25-35) in absence or presence 20 mu M DHA to evaluate its effect on the Af325_35-induced neurotoxicity by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)l-redox and TUNEL (TdT-mediated dUTP-biotin nick end-labeling) assay and immunohistochemistry. The level of A beta(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 A beta(25-35) in vitro fibrillation, as indicated by fluorospectroscopy and transmission electron microscopy. A beta(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 A beta(25-35) in the presence of DHA. MU redox potential significantly increased and the levels LPO decreased, suggesting an inhibition of the A beta(25-35)-induced neurotoxity. DHA improved the A beta(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. Conclusion: DHA not only inhibits the in vitro fibrillation but also resists the A beta(25-35)-induced toxicity in the neuronal cells. This might be the basis of the DHA-induced amelioration of A beta-induced neurodegeneration and related cognitive deficits. (C) 2011 Published by Elsevier Inc.