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Review
. 2008 Sep-Nov;79(3-5):153-6.
doi: 10.1016/j.plefa.2008.09.010. Epub 2008 Oct 29.

Brain arachidonic and docosahexaenoic acid cascades are selectively altered by drugs, diet and disease

Stanley I Rapoport  1
Affiliations
Review

Brain arachidonic and docosahexaenoic acid cascades are selectively altered by drugs, diet and disease

Stanley I Rapoport. Prostaglandins Leukot Essent Fatty Acids. 2008 Sep-Nov.

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.

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Figures

Fig. 1
Fig. 1
Model of brain arachidonic acid (AA) cascade. AA at the stereospecifically numbered-2 position of a phospholipid is liberated by activation (star) of phospholipase A2 (PLA2) at the synapse. A small fraction of the liberated AA is converted to bioactive eicosanoids. The remainder diffuses to the endoplasmic reticulum while bound to a fatty acid binding protein (FABP), from where it is converted to arachidonoyl-CoA by acyl-CoA synthetase with the consumption of 2 ATPs, then reesterified by an acyltransferase. Unesterified AA in the endoplasmic reticulum exchanges freely and rapidly with unesterified AA in plasma, into which labeled AA (AA*) has been injected. Equations for calculating kinetic parameters are shown in right lower corner. Adapted from [35].
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