Arachidonic acid metabolism in brain physiology and pathology: lessons from genetically altered mouse models

• Published in: Journal of neurochemistry Vol. 102; no. 3; pp. 577 - 586
• Main Author: Bosetti, Francesca
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.08.2007; Blackwell Publishing Ltd; Blackwell
• Subjects: Animals; Arachidonic Acid - metabolism; Biochemistry and metabolism; Biological and medical sciences; Brain - metabolism; Brain - physiopathology; Brain Diseases - genetics; Brain Diseases - metabolism; Brain Diseases - physiopathology; Central nervous system; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges; cyclooxygenase; Fundamental and applied biological sciences. Psychology; genetic models; knockout; Mice; Mice, Knockout - genetics; Mice, Knockout - metabolism; Models, Biological; neurotoxicity; phospholipase A; phospholipase A2; Phospholipases A - metabolism; prostaglandin; prostaglandin synthase; Prostaglandin-Endoperoxide Synthases - metabolism; prostaglandins; Prostaglandins - biosynthesis; Vertebrates: nervous system and sense organs; Animal model; Prostaglandin-endoperoxide synthase; phospholipase A2; Central nervous system; Phospholipid; Esterases; Synthase; Arachidonic acid; Encephalon; neurotoxicity; Eicosanoid; Development; Physiology; Neurological disorder; Release; knockout; Nervous system diseases; Enzyme; prostaglandin; Arachidonic acid derivatives; Rodentia; cyclooxygenase; Metabolism; genetic models; Phospholipase A; Carboxylic ester hydrolases; Vertebrata; Mammalia; Mouse; Mental disorder; Hydrolases; Oxidoreductases
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2007.04558.x

The arachidonic acid (AA) cascade involves the release of AA from the membrane phospholipids by a phospholipase A₂, 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 A₂/cyclooxygenases pathway, are summarized, and the specific phenotypes of genetically altered mice relevant to brain physiology and neurotoxic models are discussed.