In vivo fatty acid incorporation into brain phosholipids in relation to plasma availability, signal transduction and membrane remodeling.
A method, model, and "operational equations" are described to quantify in vivo turnover rates and half-lives of fatty acids within brain phospholipids, as well as rates of incorporation of these fatty acids into brain from plasma. In awake rats, recycling of fatty acids within brain phospholipids, due to deesterification and reesterification, is very rapid, with half-lives in some cases of minutes to hours. Plasma fatty acids make only a small contribution (2-4%) to the net quantity of fatty acids that are reesterified. This explains why many weeks are necessary to recover normal brain n-3 polyunsaturated fatty acid concentrations following their prolonged dietary deprivation. Changes in recycling of specific fatty acids in response to centrally acting drugs can help to identify enzyme targets for drug action. For example, recycling of arachidonate is specifically reduced by 80% in rats treated chronically with lithium, a drug effective against bipolar disorder; the effect reflects downregulation of gene expression of an arachidonate-specific phospholipase A2. When combined with neuroimaging (quantitative autoradiography in rodents or positron-emission tomography [PET] in macaques or humans), intravenously injected radiolabeled fatty acids can be used to localize and quantify brain PLA2-mediated signal transduction, and to examine neuroplastic remodeling of brain lipid membranes.
Rapoport
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Section on Brain Physiology and Metabolism, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA. SIR@HELIX.NIH.GOV
D000109:Acetylcholine / Q000502:physiology; D000544:Alzheimer Disease / Q000378:metabolism; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D020532:Basal Nucleus of Meynert / Q000293:injuries; D001692:Biological Transport; D001812:Blood-Brain Barrier; D001825:Body Fluid Compartments; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D002491:Central Nervous System Agents / Q000494:pharmacology; D004058:Diffusion; D004195:Disease Models, Animal; D004298:Dopamine / Q000502:physiology; D004951:Esterification; D005227:Fatty Acids / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D006207:Half-Life; D000882:Haplorhini; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008563:Membrane Lipids / Q000378:metabolism*; D008954:Models, Biological; D019579:Neocortex / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010302:Parkinson Disease, Secondary / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013378:Substantia Nigra / Q000293:injuries
D001095:Arachidonic Acids; D002491:Central Nervous System Agents; D005227:Fatty Acids; D008563:Membrane Lipids; D009419:Nerve Tissue Proteins; D010743:Phospholipids; D010741:Phospholipases A; D054467:Phospholipases A2; D000109:Acetylcholine; D004298:Dopamine