[Free radicals, polyunsaturated fatty acids, cell death, brain aging].

Neuronal death generally involves, directly or indirectly, free radical attack and peroxidation. Targets are nucleic acids, proteins, the cytoskeleton, the extracellular matrix and especially membrane polyunsaturated fatty acids. a) One example for the fundamental role of fatty acids. Dietary fatty acids, and more particularly essential polyunsaturated fatty acids, have a direct influence on the composition of cerebral membranes, and hence on their functioning. Each of the two series of polyunsaturated fatty acids plays a particular role. In animals, a deficiency in linolenic acid causes serious perturbations in the nervous system. In fact, feeding animals with oils that have a low n-3 content leads to severe abnormalities in the composition of membranes, both of the brain and other organs. The rate of recovery from these anomalies is extremely slow in the brain, but rapid in the liver. Compared to certain other organs, the nervous system is neither protected against deficiency nor has it priority in the satisfaction if its needs. A decrease in acids of the linolenic series in the membranes results in a 40% reduction of Na-K-ATPase in nerve endings and a 20% reduction in 5'-nucleotidase. It also leads to anomalies in the electroretinogram which disappear with age. This deficiency in linolenic acid has little effect on motor function and disturbes activity and emotivity only slightly, but it seriously affects learning tasks. The presence of linolenic acid in the diet confers greater resistance to certain neurotoxic substances (triethyl lead, for example). Fatty acids essential for the brain could be those with very long chains. They are probably synthesized in the liver from linolenic and linoleic acids. They can also be supplied directly by food. However, if the diet contains a large proportion of very long chain fatty acids (fish oils), the lipid composition of all organs, including the brain, is altered. During the period of brain development there is a linear relation between the polyunsaturated fatty acid content of the brain and that of the diet. The requirement in linolenic acid is 200 mg/100 g of diet (0.4% of calories). That of linoleic acid is 1,200 mg/100 g of diet (2.4% of calories). b) Peroxidation of polyunsaturated fatty acids. Arachidonic acid is released by lysis of phospholipids (it is directly toxic), its peroxidized derivatives are extremely toxic. Peroxidation of membrane lipids alters enzymatic activity, the relationship between receptor and ligand, transport, and the symmetry of the lipid bilayer.(ABSTRACT TRUNCATED AT 400 WORDS)