Ethyl-eicosapentaenoate (E-EPA) attenuates motor impairments and inflammation in the MPTP-probenecid mouse model of Parkinson's disease |
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Authors: | Luchtman D W Meng Q Song C |
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Institution: | a Department of Biomedical Sciences, University of Prince Edward Island & National Institute for Nutrisciences and Health, 550 University Avenue, Charlottetown, PEI, C1A 4P3, Canada b National Engineering Institute for the Development of Endangered Medicinal Resources in Southwest China, Guangxi Botanic Garden of Medicinal Plants, 189 Changgang Road, 530023, Nanning China |
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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. |
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Keywords: | α-LA alpha-linolenic acid 5-HT serotonin 5-HIAA 5-hydroxyindoleacetic acid AA arachidonic acid COX-2 cyclo-oxygenase-2 cPLA2 cytosolic phospholipase A2 DA dopamine DHA docosahexaenoic acid DOPAC 3 4-dihydroxyphenylacetic acid DPA docosapentaenoic acid E-EPA ethyl-eicosapentaenoate EPA eicosapentaenoic acid GLA gamma-linolenic acid HVA homovanillic acid IFN-γ interferon-gamma IL-1β interleukin-1β IL-10 interleukin-10 LA linoleic acid MPP+ 1-methyl-4-phenylpyridinium MPTP 1-methyl 4-phenyl-1 2 3 6-tetrahydropyridine MPTP-P MPTP-probenecid n-3 omega-3 n-6 omega-6 NA noradrenaline PD Parkinson's disease PPAR peroxisome proliferator-activated receptor PUFA polyunsaturated fatty acid SNpc substantia nigra pars compacta TNF-α tumor necrosis factor-α |
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