Hronic Administration of Docosahexaenoic Acid R Eicosapentaenoic Acid, but Not Arachidonic Acid, Lone or in Combination with Uridine, Increases Brain Hosphatide and Synaptic Protein Levels in Gerbils

bstract—Synthesis of phosphatidylcholine, the most abunant brain membrane phosphatide, requires three circulating recursors: choline; a pyrimidine (e.g. uridine); and a polynsaturated fatty acid. Supplementing a choline-containing iet with the uridine source uridine-5=-monophosphate (UMP) r, especially, with UMP plus the omega-3 fatty acid docosaexaenoic acid (given by gavage), produces substantial inreases in membrane phosphatide and synaptic protein levls within gerbil brain. We now compare the effects of various olyunsaturated fatty acids, given alone or with UMP, on hese synaptic membrane constituents. Gerbils received, aily for 4 weeks, a diet containing choline chloride with or ithout UMP and/or, by gavage, an omega-3 (docosahexaeoic or eicosapentaenoic acid) or omega-6 (arachidonic acid) atty acid. Both of the omega-3 fatty acids elevated major rain phosphatide levels (by 18–28%, and 21–27%) and givng UMP along with them enhanced their effects significantly. rachidonic acid, given alone or with UMP, was without efect. After UMP plus docosahexaenoic acid treatment, total rain phospholipid levels and those of each individual phoshatide increased significantly in all brain regions examined cortex, striatum, hippocampus, brain stem, and cerebellum). he increases in brain phosphatides in gerbils receiving an mega-3 (but not omega-6) fatty acid, with or without UMP, ere accompanied by parallel elevations in levels of preand ost-synaptic proteins (syntaxin-3, PSD-95 and synapsin-1) ut not in those of a ubiquitous structural protein, -tubulin. ence administering omega-3 polyunsaturated fatty acids an enhance synaptic membrane levels in gerbils, and may o so in patients with neurodegenerative diseases, especially hen given with a uridine source, while the omega-6 polyunaturated fatty acid arachidonic acid is ineffective. © 2007 BRO. Published by Elsevier Ltd. All rights reserved.