Dynamics of docosahexaenoic acid metabolism in the central nervous system:Lack of effect of chronic lithium treatment

Using a method and model developed in our laboratory to quantitatively stud y brain phospholipid metabolism, in vivo rates of incorporation and turnove r of docosahexaenoic acid in brain phospholipids were measured in awake rat s. The results suggest that docosahexaenoate incorporation and turnover in brain phospholipids are more rapid than previously assumed and that this ra pid turnover dilutes tracer specific activity in brain docoshexaenoyl-CoA p ool due to release and recycling of unlabeled fatty acid from phospholipid metabolism. Fractional turnover rates for docosahexaenoate within phosphati dylinositol, choline glycerophospholipids, ethanolamine glycerophospholipid s and phosphatidylserine were 17.7, 3.1, 1.2, and 0.2 %.h(-1), respectively . Chronic lithium treatment, at a brain level considered to be therapeutic in humans (0.6 mu mol.g(-1)), had no effect on turnover of docosahexaenoic acid in individual brain phospholipids. Consistent with previous studies fr om our laboratory that chronic lithium decreased the turnover of arachidoni c acid within brain phospholipids by up to 80% and attenuated brain phospho lipase A, activity, the lack of effect of lithium on docosahexaenoate recyc ling and turnover suggests that a target for lithium's action is an arachid onic acid-selective phospholipase A(2).