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 Alzheimerʹs disease (AD), which is characterized by fibrillar amyloid deposits in the affected brains. Here, we have investigated whether DHA-induced inhibition of Amyloid β-peptide25-35 (Aβ25-35) fibrillation limits or deteriorates the toxicity of the human neuroblastoma cells (SH-SY5Y). Experimental methods In vitro fibrillation of Aβ25-35 was performed in the absence or presence of DHA. Afterwards, SH-SY5Y cells were incubated with Aβ25-35 in absence or presence 20 μM DHA to evaluate its effect on the Aβ25-35-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 Aβ25-35-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 Aβ25-35 in vitro fibrillation, as indicated by fluorospectroscopy and transmission electron microscopy. Aβ25-35 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 Aβ25-35 in the presence of DHA, MTT redox potential significantly increased and the levels LPO decreased, suggesting an inhibition of the Aβ25-35-induced neurotoxity. DHA improved the Aβ25-35 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 Aβ25-35-induced toxicity in the neuronal cells. This might be the basis of the DHA-induced amelioration of Aβ-induced neurodegeneration and related cognitive deficits.