Omega-3 fatty acid eicospentaenoic acid attenuates MPP+-induced neurodegeneration in fully differentiated human SH- SY5Y and primary mesencephalic cells

Eicosapentaenoic acid ( EPA), a neuroactive omega-3 fatty acid, has been demonstrated to exert neuroprotective effects in experimental models of Parkinson's disease ( PD), but the cellular mechanisms of protection are unknown. Here, we studied the effects of EPA in fully differentiated human SH-SY5Y cells and primary mesencephalic neurons treated with MPP+. In both in-vitro models of PD, EPA attenuated an MPP+-induced reduction in cell viability. EPA also prevented the presence of electron-dense cytoplasmic inclusions in SH-SY5Y cells. Then, possible mechanisms of the neuroprotection were studied. In primary neurons, EPA attenuated an MPP+-induced increase in Tyrosine-related kinase B (TrkB) receptors. In SH-SY5Y cells, EPA down-regulated reactive oxygen species and nitric oxide. This antioxidant effect of EPA may have been mediated by its inhibition of neuronal NADPH oxidase and cyclo-oxygenase-2 ( COX-2), as MPP+ increased the expression of these enzymes. Furthermore, EPA prevented an increase in cytosolic phospholipase A2 ( cPLA2), an enzyme linked with COX-2 in the potentially pro-inflammatory arachidonic acid cascade. Lastly, EPA attenuated an increase in the bax:bcl-2 ratio, and cytochrome c release. However, EPA did not prevent mitochondrial enlargement or a decrease in mitochondrial membrane potential. This study demonstrated cellular mechanisms by which EPA provided neuroprotective effects in experimental PD