Rhesus monkeys given pre- and postnatal diets defi- cient in n-3 essential fatty acids develop low levels of docosahexa- enoic acid (22:6 n-3, DHA) in the cerebral cortex and retina and impaired visual function. This highly polyunsaturated fatty acid is an important component of retinal photoreceptors and brain synaptic membranes. To study the turnover of polyunsaturated fatty acids in the brain and the reversibility of n-3 fatty acid defi- ciency, we fed five deficient juvenile rhesus monkeys a fish oil diet rich in DHA and other n-3 fatty acids for up to 129 weeks. The results of serial biopsy samples of the cerebral cortex indi- cated that the changes of brain fatty acid composition began as early as 1 week after fish oil feeding and stabilized at 12 weeks. The DHA content of the phosphatidylethanolamine of the fron- tal cortex increased progressively from 3.9 + 1.2 to 28.4 + 1.7 percent of total fatty acids. The n-6 fatty acid, 22:5, abnormally high in the cerebral cortex of n-3 deficient monkeys, decreased reciprocally from 16.2 * 3.1 to 1.6 0.4%. The half-life (tl,*) of DHA in brain phosphatidylethanolamine was estimated to be 21 days. The fatty acids of other phospholipids in the brain (phosphatidylcholine, -serine, and -inositol) showed similar changes. The DHA content of plasma and erythrocyte phospho- lipids also increased greatly, with estimated half-lives of 29 and 21 days, respectively. a We conclude that monkey cerebral cortex with an abnormal fatty acid composition produced by dietary n-3 fatty acid deficiency has a remarkable capacity to change its fatty acid content after dietary fish oil, both to in- crease 22:6 n-3 and to decrease 22:5 n-6 fatty acids. The bio- chemical evidence of n-3 fatty acid deficiency was completely corrected. These data imply a greater lability of the fatty acids of the phospholipids of the cerebral cortex than has been hitherto appreciated. -Connor, W. E., M. Neuringer, and D. S. Lin. Dietary effects on brain fatty acid composition: the reversibility on n-3 fatty acid deficiency and turnover of docosahexaenoic acid in the brain, erythrocytes, and plasma of rhesus monkeys. J Lipid Res. 1990. 31: 237-247.

reversibility of n-3 fatty acid deficiency and turnover of docosahexaenoic acid in the brain, erythrocytes, and plasma of rhesus monkeys'

Dietary effects on brain fatty acid composition: the reversibility of n-3 fatty acid deficiency and turnover of docosahexaenoic acid in the brain, erythrocytes, and plasma of rhesus monkeys.

α-Linolenic acid (ALA) is a nutraceutical found in vegetable products such as flax and walnuts. The pleiotropic properties of ALA target endogenous neuroprotective and neurorestorative pathways in brain and involve the transcription factor nuclear factor kappa B (NF-κB), brain-derived neurotrophic factor (BDNF), a major neuroprotective protein in brain, and downstream signaling pathways likely mediated via activation of TrkB, the cognate receptor of BDNF. In this review, we discuss possible mechanisms of ALA efficacy against the highly toxic OP nerve agent soman. Organophosphate (OP) nerve agents are highly toxic chemical warfare agents and a threat to military and civilian populations. Once considered only for battlefield use, these agents are now used by terrorists to inflict mass casualties. OP nerve agents inhibit the critical enzyme acetylcholinesterase (AChE) that rapidly leads to a cholinergic crisis involving multiple organs. Status epilepticus results from the excessive accumulation of synaptic acetylcholine which in turn leads to the overactivation of muscarinic receptors; prolonged seizures cause the neuropathology and long-term consequences in survivors. Current countermeasures mitigate symptoms and signs as well as reduce brain damage, but must be given within minutes after exposure to OP nerve agents supporting interest in newer and more effective therapies. The pleiotropic properties of ALA result in a coordinated molecular and cellular program to restore neuronal networks and improve cognitive function in soman-exposed animals. Collectively, ALA should be brought to the clinic to treat the long-term consequences of nerve agents in survivors. ALA may be an effective therapy for other acute and chronic neurodegenerative disorders.

α-Linolenic Acid, A Nutraceutical with Pleiotropic Properties That Targets Endogenous Neuroprotective Pathways to Protect against Organophosphate Nerve Agent-Induced Neuropathology

Humans need fat in the diet in order to survive, grow, and prosper. Over 60 yr ago, Burr and Burr demonstrated that fat was an essential component of the diet (1929). Rats reared on a fat-free diet failed to grow and reproduce and also developed renal disease, fatty liver, dermatitis, and necrosis of the tail. Later studies identified the deficient components of the diet as the polyunsaturated fatty acids with two or more double bonds (Holman, 1968). Until recently, linoleic acid, an 18:2\n-6 fatty acid commonly found in vegetable oils and many other foods, was deemed the primary essential fatty acid, together with its derivative n-6 fatty acids, of which arachidonic acid (20:4) was the most important. The second series of highly polyunsaturated fatty acids includes the n-3 fatty acids, a-linolenic acid (18:3) and its longer-chained, more polyunsaturated derivative, docosahexaenoic acid (22:6). n-3 Fatty acids are also contained in a wide variety of natural foodstuffs, including some but not all liquid vegetable oils, particularly soybean and rapeseed oils, and green leafy vegetables. The higher n-3 fatty acid derivative, docosahexaenoic acid, is found particularly in plants of the sea, phytoplankton, or, as one ascends the food chain, in shellfish, fish, and sea mammals and in the tissues of terrestrial animals but not in land plants. Docosahexaenoic acid is especially predominant in the brain, retina, and spermatozoa but is also found in phospholipid membranes throughout the body, including the myocardium (Lin et al., 1993). It now appears that both n-6 and n-3 fatty acids are essential for health.

Dietary N-3 Fatty Acid Deficiency and Its Reversibility

Weanling rats have been fed different diets containing hydrogenated coconut oil or a mixture of grapestone + linseed oil as dietary fats. Groups of 12 animals have been sacrificed at weanling or after 60 or 120 days of this dietary treatment. Body and brain weight, brain total lipids, phospholipids, cholesterol, cerebroside, fatty acid content and fatty acid composition have been evaluated. The diet rich in alphalinolenic acid (C 18:3 n-3) induced a significant increase of the n-3 polyunsaturated fatty acids (C 22:5 and C 22:6, n-3) in the brain, with respect to the other experimental conditions.

Carpigiani M

Papers

Effect of C 18:3 (n-3) dietary supplementation on the fatty acid composition of the rat brain.