Arachidonic Acid and the Brain 1-3

Kinetic methods in unanesthetized rodents have shown that turnover rates of arachidonic acid (AA) and docosahexaenoic acid(DHA)inbrainmembranephospholipidsarerapidandenergyconsumingandthatphospholipaseA2(PLA2)andacyl-CoA synthetaseenzymesthat regulateturnoverare specificfor one or the otherPUFA. Thus, AA turnover in brain phospholipids was reduced, and AA-selective cytosolic cPLA2 or acyl-CoA synthetase, as well as cyclooxygenase (COX)-2, were downregulated in brains of rats given drugs effective against bipolar disorder, whereas DHA turnover and expression of DHA-selective calcium-independent iPLA2 were unchanged. Additionally, the brain AA and DHA cascades can be altered reciprocallybydietaryorgeneticconditions.Thus,following15wkofdietary(n-3)PUFAdeprivation,DHAlossfromratbrain was slowed because of reduced iPLA2 and COX-1 expression, whereas AA-selective cPLA2, sPLA2, and COX-2 were upregulated,aswereAAanddocosapentaenoicacidconcentrations.MeasuredratesofAAandDHAincorporationintobrain represent their respective rates of metabolic consumption, because these PUFA are not synthesized de novo or converted significantly from their precursors in brain. In healthy human volunteers, positron emission tomography (PET) was used to show that the brain consumes AA and DHA at respective rates of 17.8 and 4.6 mg/d, whereas in patients with Alzheimer disease, AA consumption is elevated. In the future, PET could be used to relate human brain rates of AA and DHA consumption to liver PUFA metabolism and dietary PUFA intake. J. Nutr. 138: 2515‐2520, 2008.