title: ω-3 fatty acid eicosapentaenoic acid attenuates MPP+-induced neurodegeneration in fully differentiated human SH-SY5Y and primary mesencephalic cells.
abstract: 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.
authors.affiliation: National Research Institute for Nutrisciences and Health and Department of Biomedical Science, University of Prince Edward Island, Charlottetown, Canada.
authors.forename: Dirk W
authors.initials: DW
authors.lastname: Luchtman
authors.forename: Qingjia
authors.initials: Q
authors.lastname: Meng
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Wang
authors.forename: Di
authors.initials: D
authors.lastname: Shao
authors.forename: Cai
authors.initials: C
authors.lastname: Song
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D015118:Eicosapentaenoic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008636:Mesencephalon / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D015525:Fatty Acids, Omega-3; D018696:Neuroprotective Agents; D015118:Eicosapentaenoic Acid; D015655:1-Methyl-4-phenylpyridinium