Abstract

BACKGROUND:

The n-3 polyunsaturated fatty acid, eicosapentaenoic acid (EPA) has been found to process neuroprotective effects. However, the exact cellular mechanisms are not well understood. Brain-derived neurotrophic factor (BDNF) is one of neurotrophins, which is involved in neuron differentiation, survival, and synaptogenesis.

AIM OF THE STUDY:

In this study, the potential neuroprotective effects of EPA, and its possible effects on BDNF and BDNF receptor expression were investigated in SH-SY5Y cells.

METHODS:

Both undifferentiated and retinoic acid (RA)-BDNF differentiated SH-SY5Y cells were treated with EPA and/or BDNF. The cell viability was determined by MTT assay. The expression of BDNF receptors, tyrosine kinase receptor B (TrkB) and p75(NTR) were tested by RT-PCR and Western blotting.

RESULTS:

In undifferentiated SH-SY5Y cells, either EPA or BDNF, or both did not affect the cell viability. In RA-BDNF differentiated SH-SY5Y cells, treatment with different doses of EPA (0.01, 0.1, 1.0, 10.0 microM) and BDNF (1 ng/ml) for 24 hours significantly increased the cell viability, while EPA or BDNF alone showed no effect. More importantly, RT-PCR and Western blotting results revealed that 24 hours treatment with EPA (0.01, 0.1, 1.0 microM) significantly increased the full-length TrkB (TrkB(TK+)), but not truncated TrkB (TrkB(TK-)) expression in these cells. An increase in p75(NTR) expression was also observed with 10.0 microM EPA treatment. Finally, co-incubation with either 100 nM staurosporine, a protein kinase inhibitor, or 500 nM K252a, a tyrosine kinase inhibitor completely abolished the EPA-induced increase in cell viability.

CONCLUSIONS:

Our results indicate that EPA exerts beneficial effects on cell survival through modulating neurotrophin receptor expression.