Abstract
Cyclooxygenase (COX)-2 plays an important role in brain arachidonic acid (20:4n-6) metabolism, and its expression is upregulated in animal models of neuroinflammation and excitotoxicity. Our hypothesis was that brain lipid composition would be altered in COX-2 knockout (COX-2(-/-)) compared with wild-type (COX-2(+/+)) mice, reflecting the important role of COX-2 in brain lipid metabolism. Concentrations of different lipids were measured in high-energy microwaved brain from COX-2(-/-) and COX-2(+/+) mice. Compared with the COX-2(+/+) mouse brain, the brain of the COX-2(-/-) mouse had a statistically significant 15% increase in phosphatidylserine (PtdSer) and significant 37, 27, and 32% reductions in triacylglycerol and cholesterol concentrations and in the cholesterol-to-phospholipid ratio, respectively. The normalized concentration of palmitic acid (16:0) was increased in PtdSer, as was the brain concentration of unesterified arachidic acid (20:0). A lifetime absence of COX-2 produces multiple changes in brain lipid composition. These changes may be related to reported changes in fatty acid kinetics and in resistance to neuroinflammation and excitotoxicity in the COX-2(-/-) mouse.
Highlights
Cyclooxygenase (COX)-2 plays an important role in brain arachidonic acid (20:4n-6) metabolism, and its expression is upregulated in animal models of neuroinflammation and excitotoxicity
The brain concentration of PtdSer was increased significantly by 15% in the COX-22/2 mouse, whereas concentrations of ethanolamine glycerophospholipid (EtnGpl), choline glycerophospholipid (ChoGpl), PtdIns, and CerPCho did not differ significantly between groups (Table 1)
Brain lipid composition was altered in several ways in the COX-22/2 compared with the COX-21/1 mouse
Summary
Cyclooxygenase (COX)-2 plays an important role in brain arachidonic acid (20:4n-6) metabolism, and its expression is upregulated in animal models of neuroinflammation and excitotoxicity. Not part of this study, we reported previously that there was no statistically significant difference in the mean concentrations of plasma palmitic (16:0), palmitoleic (16:1n-7), stearic (18:0), oleic (18:1n-9), linoleic (18:2n-6), a-linolenic (18:3n-3), arachidonic (20:4n-6), or docosahexaenoic (22:6n-3) acid between unanesthetized COX-22/2 and COX-21/1 mice [5].
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