title: Ethyl-eicosapentaenoate (E-EPA) attenuates motor impairments and inflammation in the MPTP-probenecid mouse model of Parkinson's disease.
abstract: Parkinson's disease (PD) is a neurodegenerative disorder, characterized by hypokinesia, but also mood and cognitive disorders. Neuropathologically, PD involves loss of nigrostriatal dopamine (DA) and secondary non-dopaminergic abnormalities. Inflammation may contribute to PD pathogenesis, evident by increased production of pro-inflammatory cytokines. PD onset has been positively associated with dietary intake of omega-(n)-6 polyunsaturated fatty acids (PUFA). On the other hand, omega-(n)-3 PUFA may benefit PD. One of these n-3 PUFA, eicosapentaenoic acid (EPA), is a neuroprotective lipid with anti-inflammatory properties, but its neuroprotective effects in PD are unknown. Thus, we presently tested the hypothesis that EPA can protect against behavioral impairments, neurodegeneration and inflammation in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-probenecid (MPTP-P) mouse model of PD. MPTP-P injections caused hypokinesia in the rotorod and pole test, hyperactivity in the open field, and impaired mice on the cued version (procedural memory) of the Morris water maze. MPTP-P caused a loss of nigrostriatal DA and altered neurochemistry in the frontal cortex and hippocampus. Furthermore, striatal levels of pro-inflammatory cytokines were increased, while the brain n-3/n-6 lipid profile remained unaltered. Feeding mice a 0.8% ethyl-eicosapentaenoate (E-EPA) diet prior to MPTP-P injections increased brain EPA and docosapentaenoic acid (DPA) but not docosahexaenoic acid (DHA) or n-6 PUFA. The diet attenuated the hypokinesia induced by MPTP-P and ameliorated the procedural memory deficit. E-EPA also suppressed the production of pro-inflammatory cytokines. However, E-EPA did not prevent nigrostriatal DA loss. Based on this partial protective effect of E-EPA, further testing may be warranted.
authors.affiliation: Department of Biomedical Sciences, University of Prince Edward Island & National Institute for Nutrisciences and Health, 550 University Avenue, Charlottetown, PEI, C1A 4P3, Canada.
authors.forename: D W
authors.initials: DW
authors.lastname: Luchtman
authors.forename: Q
authors.initials: Q
authors.lastname: Meng
authors.forename: C
authors.initials: C
authors.lastname: Song
mesh_terms: D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D016207:Cytokines / Q000378:metabolism; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005106:Exploratory Behavior / Q000187:drug effects; D015525:Fatty Acids, Omega-3 / Q000378:metabolism; D043371:Fatty Acids, Omega-6 / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000178:diet therapy*; D020267:MPTP Poisoning / Q000178:diet therapy*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000178:diet therapy*; D054510:Phospholipases A2, Cytosolic / Q000096:biosynthesis; D011339:Probenecid; D045442:Rotarod Performance Test / Q000706:statistics & numerical data*
chemical_list: D015306:Biogenic Monoamines; D016207:Cytokines; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D018696:Neuroprotective Agents; C035276:eicosapentaenoic acid ethyl ester; D015118:Eicosapentaenoic Acid; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D054510:Phospholipases A2, Cytosolic; D011339:Probenecid