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). EXPERIMENTAL 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. CONCLUSION: 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.
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 humanneuroblastoma cells (SH-SY5Y). EXPERIMENTAL 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. CONCLUSION: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.
Authors: Edmond Teng; Karen Taylor; Tina Bilousova; David Weiland; Thaidan Pham; Xiaohong Zuo; Fusheng Yang; Ping-Ping Chen; Charles G Glabe; Alison Takacs; Dennis R Hoffman; Sally A Frautschy; Gregory M Cole Journal: Neurobiol Dis Date: 2015-09-12 Impact factor: 5.996