Arachidonic acid and the brain.
Kinetic methods in unanesthetized rodents have shown that turnover rates of arachidonic acid (AA) and docosahexaenoic acid (DHA) in brain membrane phospholipids are rapid and energy consuming and that phospholipase A(2) (PLA(2)) and acyl-CoA synthetase enzymes that regulate turnover are specific for one or the other PUFA. Thus, AA turnover in brain phospholipids was reduced, and AA-selective cytosolic cPLA(2) 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 iPLA(2) were unchanged. Additionally, the brain AA and DHA cascades can be altered reciprocally by dietary or genetic conditions. Thus, following 15 wk of dietary (n-3) PUFA deprivation, DHA loss from rat brain was slowed because of reduced iPLA(2) and COX-1 expression, whereas AA-selective cPLA(2), sPLA(2), and COX-2 were upregulated, as were AA and docosapentaenoic acid concentrations. Measured rates of AA and DHA incorporation into brain 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.
Rapoport
Stanley I
SI
Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA. sir@helix.nih.gov
D000818:Animals; D018692:Antimanic Agents / Q000008:administration & dosage; D016718:Arachidonic Acid / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D004281:Docosahexaenoic Acids / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage; D006801:Humans; D007700:Kinetics; D008094:Lithium / Q000008:administration & dosage; D008959:Models, Neurological; D054467:Phospholipases A2 / Q000378:metabolism; D049268:Positron-Emission Tomography; D051381:Rats; D015854:Up-Regulation / Q000187:drug effects
D018692:Antimanic Agents; D015525:Fatty Acids, Omega-3; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D008094:Lithium; D054467:Phospholipases A2