Cyclooxygenase-2 and n-6 PUFA are lower and DHA is higher in the cortex of fat-1 mice.
Neuroinflammation is believed to play an important role in neurological diseases such as Alzheimer's disease (AD). Growing evidence suggests that n-3 PUFA have protective effects by inhibiting inflammatory processes including synthesis of eicosanoids from arachidonic acid. There is also some evidence suggesting that inflammatory mediators associated with the arachidonic acid cascade may be modulated by n-3 PUFA in healthy animals. Therefore, in this study, the effect of n-3 PUFA on brain cortex fatty acid composition, and on the expression of calcium-dependant cytosolic phospholipase A(2) (cPLA(2)) and cyclooxygenase-2 (COX-2) was assessed in the transgenic fat-1 mouse. Phospholipid fatty acid composition was determined by thin layer and gas chromatography, while cortical cPLA(2) and COX-2 were determined by Western blotting. 22:6 n-3 levels were up to 220% higher while n-6 PUFA levels were up to 77% lower in fat-1 phospholipid fractions of the cortex as compared to wildtype (WT) mice. COX-2 protein levels were 25% lower in fat-1 as compared to WT mice (p=0.02), but cPLA(2) expression levels did not change. Our results suggest that this model could be used to investigate mechanisms by which n-3 PUFA regulate neuroinflammation.
Boudrault
Cynthia
C
Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Canada.
Bazinet
Richard P
RP
Kang
Jing X
JX
Ma
David W L
DW
D000199:Actins / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D002849:Chromatography, Gas; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D043371:Fatty Acids, Omega-6 / Q000378:metabolism* / Q000494:pharmacology*; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D008297:Male; D008745:Methylation; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010641:Phenotype; D054467:Phospholipases A2 / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism
D000199:Actins; D015820:Cadherins; D043371:Fatty Acids, Omega-6; D010743:Phospholipids; C502406:fat1 protein, mouse; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D051546:Cyclooxygenase 2; D054467:Phospholipases A2