Ethyl-eicosapentaenoate modulates changes in neurochemistry and brain lipids induced by parkinsonian neurotoxin 1-methyl-4-phenylpyridinium in mouse brain slices.
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.
Meng
QingJia
Q
Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island, and Institute for Nutrisciences and Health, National Research Council of Canada, 550 University Avenue, Charlottetown, PE, Canada C1A 4P3. carmen0070@hotmail.com
Luchtman
Dirk W
DW
El Bahh
Bouchaib
B
Zidichouski
Jeffrey A
JA
Yang
Jun
J
Song
Cai
C
D015655:1-Methyl-4-phenylpyridinium / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000378:metabolism; D043371:Fatty Acids, Omega-6 / Q000378:metabolism; D005625:Frontal Lobe / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control*; D054510:Phospholipases A2, Cytosolic / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D018836:Inflammation Mediators; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C035276:eicosapentaenoic acid ethyl ester; D015118:Eicosapentaenoic Acid; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D054510:Phospholipases A2, Cytosolic; D015655:1-Methyl-4-phenylpyridinium