The brain is roughly fifty percent lipid, with polyunsaturates making up 35% of the total fatty acids. The brain and retina, and in particular the synaptic membranes and rod outer segments, are especially rich in the n-3 family of polyunsaturated fatty s. Nutritional studies in animals have identified numerous abnormalities when n-3 fatty acids are deficient in the diet. These include reduced visual acuity, impaired learning, altered behavior, and effects on sleep. The process by which these critical polyunsaturated fatty acids reach the brain is unclear. The long-term objective of this research is to characterize the transport and uptake of lipids, particularly n-3 fatty acids, into the brain, and to examine the nutritional qualities of n-3 fatty acids and their role in the brain. The n-3 fatty acids have also recently become the focus of research as regards their possible prevention of coronary heart disease. The transport and uptake of lipids by the brain will be studied first in the two-week old rat, whose brain is rapidly accumulating polyunsaturated fatty acids. Intravenous injection of radiolabeled saturated, n-6, and n-3 fatty acids, contained in phospholipids, chylomicrons, and as free fatty acids, will test whether there is a preferred chemical form for """"""""brain-destined"""""""" fatty acids. Previous experiments showing a preferential uptake by the brain of n-3 fatty acids will expanded by examining the developmental course of uptake and the effect of diet. In addition, the possible role of the liver will be examined by functionally hepatectomizing some of the animals. The nutritional qualities of individual n-3 fatty acids and the role of 22:6n-3 in the brain will be studied in n-3 fatty acid deficient chicks. Chicks are an especially useful model because of the speed with which the fatty acid composition of eggs (and thus the resulting chick tissues, including the brain) can be manipulated through the feeding of an n-3 fatty acid-free diet to laying hens. 18:3n-3, 20:5n-3, and 22:6n-3 will be fed to these virtually n-3 fatty acid-free chicks, and the relative effects on brain, retina, and serum fatty acid composition will be studied. Also, the reversibility of 22:6n-3 feeding will be examined in these tissues. The role of n-3 fatty acids in the brain will be probed by determining the effects of the deficiency on brain phospholipid molecular species composition, brain enzyme activities (ethanolaminephosphotransferase, phosphatidylethanolamine methyltransferase, 5'-nucleotidase), growth, and reproduction.
