This article is available online at http://www.jlr.org disease, Parkinson's disease, bipolar disorder, and major depression ( 7-9 ).ARA and DHA can either be obtained directly from the diet or synthesized from their nutritionally essential precursor fatty acids linoleic acid (18:2n-6; LA) and ␣ -linolenic acid (18:3n-3; ALA) respectively, which are the main dietary n-6 and n-3 PUFAs. Thus, it is of interest to determine whether changes in the level of dietary n-6 or n-3 PUFAs can alter the concentrations of ARA and/or DHA in the brain, and more importantly, whether these dietary changes affect their metabolism. In fact, clinical trials in humans are underway, with the assumption that lowering n-6 PUFAs may decrease brain ARA and its metabolism ( 1 ).Several studies have investigated the effects of dietary n-3 PUFA deprivation on brain ARA and DHA concentrations and metabolism in rats. Feeding rats an n-3 PUFAdeprived diet that contains ALA at a concentration of 0.04% versus an n-3 PUFA-adequate diet containing ALA at 4.4% of all fatty acids decreased the concentration of DHA by 37% and increased docosapentaenoic acid (DPA) n-6 concentration by 95% in brain total phospholipids, but did not change the concentration of ARA ( 10 ). This study also reported that n-3 PUFA deprivation conserves DHA in rat brain phospholipids extending the half-life from 33 to 90 days. This conservation response was selective for DHA, as n-3 PUFA deprivation did not alter the half-life or rate of ARA metabolic consumption ( 11 ). Alterations in brain DHA concentration and metabolism appear to occur below a threshold of 0.8% ALA in the diet, Abstract To determine how the level of dietary n-6 PUFA affects the rate of loss of arachidonic acid (ARA) and DHA in brain phospholipids, male rats were fed either a deprived or adequate n-6 PUFA diet for 15 weeks postweaning, and then subjected to an intracerebroventricular infusion of 3 H-ARA or 3 H-DHA. Brains were collected at fi xed times over 128 days to determine half-lives and the rates of loss from brain phospholipids ( J out ). Compared with the adequate n-6 PUFA rats, the deprived n-6-PUFA rats had a 15% lower concentration of ARA and an 18% higher concentration of DHA in their brain total phospholipids. Loss half-lives of ARA in brain total phospholipids and fractions (except phosphatidylserine) were longer in the deprived n-6 PUFA rats, whereas the J out was decreased. In the deprived versus adequate n-6 PUFA rats, the J out of DHA was higher. In conclusion, chronic n-6 PUFA deprivation decreases the rate of loss of ARA and increases the rate of loss of DHA in brain phospholipids. Thus, a low n-6 PUFA diet can be used to target brain ARA and DHA metabolism. The brain is specifi cally enriched with the two PUFAs arachidonic acid (20:4n-6; ARA) and DHA (22:6n-3), which are considered important for normal brain function. Bioactive mediators from ARA and DHA, the eicosanoids and docosanoids, respectively, regulate many processes including neuroinfl ammation, pain perception, and blood fl ow...

Multiple sclerosis is a demyelinating and inflammatory disease. Myelin is enriched in lipids, and more specifically, oleic acid. The goal of this study was to evaluate the concentration of oleic acid following demyelination and remyelination in the cuprizone model, test if these changes occurred in specific lipid species, and whether differences in the cuprizone model correlate with changes observed in post-mortem human brains. Eight-week-old C57Bl/6 mice were fed a 0.2% cuprizone diet for 5 weeks and some animals allowed to recover for 11 days. Demyelination, inflammation, and lipid concentrations were measured in the corpus callosum. Standard fatty acid techniques and liquid chromatography combined with tandem mass spectrometry were performed to measure concentrations of fatty acids in total brain lipids and a panel of lipid species within the phosphatidylcholine (PC). Similar measurements were conducted in post-mortem brain tissues of multiple sclerosis patients and were compared to healthy controls. Five weeks of cuprizone administration resulted in demyelination followed by significant remyelination after 11 days of recovery. Compared to control, oleic acid was decreased after 5 weeks of cuprizone treatment and increased during the recovery phase. This decrease in oleic acid was associated with a specific decrease in the PC 36:1 pool. Similar results were observed in human post-mortem brains. Decreases in myelin content in the cuprizone model were accompanied by decreases in oleic acid concentration and is associated with PC 36:1 suggesting that specific lipids could be a potential biomarker for myelin degeneration. The biological relevance of oleic acid for disease progression remains to be verified.