title: Brain arachidonic and docosahexaenoic acid cascades are selectively altered by drugs, diet and disease.
abstract: Metabolic cascades involving arachidonic acid (AA) and docosahexaenoic acid (DHA) within brain can be independently targeted by drugs, diet and pathological conditions. Thus, AA turnover and brain expression of AA-selective cytosolic phospholipase A(2) (cPLA(2)), but not DHA turnover or expression of DHA-selective Ca(2+)-independent iPLA(2), are reduced in rats given agents effective against bipolar disorder mania, whereas experimental excitotoxicity and neuroinflammation selectively increase brain AA metabolism. Furthermore, the brain AA and DHA cascades are altered reciprocally by dietary n-3 polyunsaturated fatty acid (PUFA) deprivation in rats. DHA loss from brain is slowed and iPLA(2) expression is decreased, whereas cPLA(2) and COX-2 are upregulated, as are brain concentrations of AA and its elongation product, docosapentaenoic acid (DPA). Positron emission tomography (PET) has shown that the normal human brain consumes 17.8 and 4.6 mg/day, respectively, of AA and DHA, and that brain AA consumption is increased in Alzheimer disease patients. In the future, PET could help to determine how human brain AA or DHA consumption is influenced by diet, aging or disease.
authors.affiliation: Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Building 9, Room 1S128, 9 Memorial Drive, Bethesda, MD 20892, USA. sir@helix.nih.gov
authors.forename: Stanley I
authors.initials: SI
authors.lastname: Rapoport
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D001714:Bipolar Disorder / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D004032:Diet; D004041:Dietary Fats / Q000008:administration & dosage; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage; D006801:Humans; D008954:Models, Biological; D049268:Positron-Emission Tomography; D051381:Rats; D015854:Up-Regulation
chemical_list: D004041:Dietary Fats; D015525:Fatty Acids, Omega-3; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid