Ethyl-eicosapentaenoate modulates changes in ...
|Title||Ethyl-eicosapentaenoate modulates changes in neurochemistry and brain lipids induced by parkinsonian neurotoxin 1-methyl-4-phenylpyridinium in mouse brain slices|
|Author(s)||QingJia Meng, Dirk W. Luchtman, Bouchaib El Bahh, Jeffrey A. Zidichouski, Jun Yang, Cai Song|
|Journal||European Journal of Pharmacology|
|Abstract||Evidence suggests a link between Parkinson's disease and the dietary intake of omega (n)−3 and n−6 polyunsaturated fatty acids (PUFAs). Presently, we investigated whether an acute dose of parkinsonian neurotoxin 1-methyl-4-phenylpyridinium (MPP+) affects brain n−3 and n−6 PUFA content and expression of fatty acid metabolic enzymes cytosolic phospholipase A2 (cPLA2) and cyclooxygenase-2 (COX-2) in brain slices from C57Bl/6 mice. Furthermore, we investigated whether feeding a diet of n−3 PUFA ethyl-eicosapentaenoate (E-EPA) to these mice can attenuate the MPP+ induced changes in brain PUFA content and expression of cPLA2 and COX-2, and attenuate MPP+ induced changes in neurotransmitters and metabolites and apoptotic markers, bax, bcl-2 and caspase-3. MPP+ increased brain content of n−6 PUFAs linoleic acid and arachidonic acid, and increased the mRNA expression of cPLA2. MPP+ also depleted striatal dopamine levels and increased dopamine turnover, and depleted noradrenaline levels in the frontal cortex. The neurotoxin induced increases in bax, bcl-2 and caspase-3 mRNA expression that approached significance. E-EPA by itself increased brain n−3 content, including EPA and docosapentaenoic acid (C22:5, n−3), and increased cortical dopamine. More importantly, E-EPA attenuated the MPP+ induced increase in n−6 fatty acids content, partially attenuated the striatal dopaminergic turnover, and prevented the increases of pro-apoptotic bax and caspase-3 mRNAs. In conclusion, increases in n−6 PUFAs in the acute stage of exposure to parkinsonian neurotoxins may promote pro-inflammatory conditions. EPA may provide modest beneficial effects in Parkinson's disease, but further investigation is warranted.|
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