Effect of Docosahexaenoic Acid on the Synthesis of Phosphatidylserine in Rat Brain Microsomes and C6 Glioma Cells

Abstract: Docosahexaenoic acid (22:6n‐3) is the major polyunsaturated fatty acid (PUFA) in the CNS and accumulates particularly in phosphatidylserine (PS). We have investigated the effect of the 22:6n‐3 compositional status on the synthesis of PS. The fatty acid composition of brain microsomes from offspring of rats artificially reared on an n‐3‐deficient diet showed a dramatic reduction of 22:6n‐3 content (1.7 ± 0.1%) when compared with control animals (15.0 ± 0.2%). The decrease was accompanied by an increase in docosapentaenoic acid (22:5n‐6) content, which replaced the 22:6n‐3 phospholipids with 22:5n‐6 molecular species, as demonstrated using HPLC/electrospray mass spectrometry. The n‐3 deficiency did not affect the total amount of polyunsaturated phospholipids in brain microsomes; however, it was associated with a decrease in the total polyunsaturated PS content and with increased levels of 1‐stearoyl‐2‐docosapentanoyl (18:0/22:5n‐6) species, particularly in phosphatidylcholine. Incorporation of [3H]serine into PS in rat brain microsomes from n‐3‐deficient animals was slightly but significantly less than that of the control animals. Similarly, C6 glioma cells cultured for 24 h in 22:6n‐3‐supplemented media (10–40 µM) showed a significant increase in the synthesis of [3H]PS when compared with unsupplemented cells. Our data show that neuronal and glial PS synthesis is sensitive to changes in the docosahexaenoate levels of phospholipids and suggest that 22:6n‐3 may be a modulator of PS synthesis.