Modeling transport dynamics

     

Recycling of fatty acids within brain phospholipids is very rapid (half-lives of minutes to hours). Plasma fatty acids make only a small contribution (2-4%) to the net quantity of fatty acids reesterified, making many weeks necessary to restore n-3 PUFA concentrations after prolonged dietary deprivation. Changes in recycling in response to centrally acting drugs help 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. Neuroimaging (quantitative autoradiography in rodents or positron-emission tomography [PET ] in macaques or humans) with intravenously injected radiolabeled fatty acids can localize and quantify neuroplastic remodeling of brain lipid membranes. Rapoport SI. In vivo fatty acid incorporation into brain phosholipids in relation to plasma availability, signal transduction and membrane remodeling. J Mol Neurosci 2001 Apr-Jun;16(2-3):243-61; discussion 279-84

      Calculations for adult rats show that 3-5% of esterified brain arachidonic acid (AA) and 2-8% of esterified brain docosahexaenoic acid (DHA) are replaced daily by unesterified PUFAs in plasma, suggesting half-lives of 1-2 weeks for plasma-brain exchange of AA and DHA. In the human brain, the arachidonate replacement rate of 0.3% per day is sufficient to compensate for metabolic and efflux losses and make PUFA transport from plasma into brain unnecessary. Rapoport SI, Chang MC, Spector AA. Delivery and turnover of plasma-derived essential PUFAs in mammalian brain. J Lipid Res 2001 May;42(5):678-685.

     An in vivo method allows quantification and imaging of fatty acid incorporation into different brain phospholipids in relation to membrane synthesis, neuroplasticity, and signal transduction. The method can be used with positron emission tomography. Rapoport SI, Purdon D, Shetty HU, Grange E, Smith Q, Jones C, Chang MC. In vivo imaging of fatty acid incorporation into brain to examine signal transduction and neuroplasticity involving phospholipids. Ann N Y Acad Sci 1997 May 30;820:56-73; discussion 73-4