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J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.M600400-JLR200 on January 3, 2007

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Journal of Lipid Research, Vol. 48, 848-854, April 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology

Altered brain lipid composition in cyclooxygenase-2 knockout mouse

Kaizong Ma*, Robert Langenbach{dagger}, Stanley I. Rapoport* and Mireille Basselin1,*

* Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892
{dagger} National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709

Published, JLR Papers in Press, January 3, 2007.

1 To whom correspondence should be addressed. e-mail: mirvasln{at}mail.nih.gov

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.

Supplementary key words fatty acids • cholesterol • phosphatidylserine

Abbreviations: AA, arachidonic acid; CerPCho, sphingomyelin; ChoGpl, choline glycerophospholipid; COX, cyclooxygenase; cPLA2, cytosolic phospholipase A2; EtnGpl, ethanolamine glycerophospholipid; FAME, fatty acid methyl ester; PtdCho, phosphatidylcholine; PtdEtn, phosphatidylethanolamine; PtdIns, phosphatidylinositol; PtdSer, phosphatidylserine; sPLA2, secretory phospholipase A2


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