Arachidonic acid metabolism in brain physiology and pathology: lessons from genetically altered mouse models.
The arachidonic acid (AA) cascade involves the release of AA from the membrane phospholipids by a phospholipase A(2), followed by its subsequent metabolism to bioactive prostanoids by cyclooxygenases coupled with terminal synthases. Altered brain AA metabolism has been implicated in neurological, neurodegenerative, and psychiatric disorders. The development of genetically altered mice lacking specific enzymes of the AA cascade has helped to elucidate the individual roles of these enzymes in brain physiology and pathology. The roles of AA and its metabolites in brain physiology, with a particular emphasis on the phospholipase A(2)/cyclooxygenases pathway, are summarized, and the specific phenotypes of genetically altered mice relevant to brain physiology and neurotoxic models are discussed.
Bosetti
Francesca
F
Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA. frances@mail.nih.gov
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D001927:Brain Diseases / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D010741:Phospholipases A / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis
D011453:Prostaglandins; D016718:Arachidonic Acid; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A