n-3 fatty acid deficiency decreases phosphatidylserine accumulation selectively in neuronal tissues

We have previously shown that the docosahexaenoate (22:6n-3) status in memb rane phospholipids influences the biosynthesis and accumulation of phosphat idylserine (PS) in brain microsomes and C6 glioma cells. In the present stu dy, we investigated whether the observed effect of membrane docosahexaenoic acid status on PS accumulation is universal or occurs specifically in neur onal tissues. We observed that rat brain cortex, brain mitochondria, and ol factory bulb, where 22.6n-3 is highly concentrated, contain significantly h igher levels of PS in comparison to liver and adrenal, where 22:6n-3 is a r ather minor component. Phospholipid molecular species analysis revealed tha t in brain cortex, mitochondria, and olfactory bulb 18:0,22:6n-3 was the mo st abundant species representing 45-65% of total PS. In nonneuronal tissues such as liver and adrenal, 18:0,20:4n-6 was the major PS species. Dietary depiction of n-3 fatty acids during prenatal and postnatal developmental pe riods decreased the brain 22:6n-3 content by more than 80%, with a concomit ant increase in 22:5n-6 in all tissues. Under these conditions, an approxim ately 30-35% reduction in total PS in rat brain cortex, brain mitochondria, and olfactory bulb was observed, while PS levels in liver and adrenal were unchanged. The observed reduction of PS content in neuronal membranes appe ars to be due to a dramatic reduction of 18:0,22:6n-3-PS without complete r eplacement by 18:0,22:5n-6-PS. These results establish that variations in m embrane 22:6n-3 fatty acid composition have a profound influence on PS accu mulation in neuronal tissues where 22:6n-3 is abundant. These data have imp lications in neuronal signaling events where PS is believed to play an impo rtant role.