Docosahexaenoic acid （DHA） is one of the major long chain polyunsaturated fatty acids normally occurring in mammals and fishes. It is found in the highest concentration in the brain and a structural component of neuronal membranes. DHA is localized in the 2-position of membrane phospholipids, especially in phosphatidylethanolamine and may exert considerable influence on the membrane fluidity and functional properties of integral proteins. It has become apparent that a deficiency in DHA is associated with a loss of discriminant learning ability and visual acuity. Moreover, the patients with Alzheimer's disease show extremely low levels of DHA in their brain. However, less data are available on the action of DHA in membrane phospholipids, and little is known about the mechanism by which DHA affects several functions after release by phospholipase A2.　Much attention has been focused on the N ‐ methyl ‐ D ‐aspartate （NMDA） receptor because of its role in long-term potentiation （LTP）. The action of DHA on the functional responses to NMDA was examined in neurons acutely isolated from rat in whole-cell and single-channel modes under voltage-clamp condition. DHA potentiated the NMDA response in a concentration-dependent manner. Moreover we investigated the effect of DHA on BEL （bromoenol lactone, an iPLA2 ‐ inhibitor） ‐ impaired LTP, and found that DHA abolished the effect of BEL. Linoleic acid had no effects, either.　These results suggest that DHA is crucial for the induction of LTP and that endogenously released DHA during tetanus is sufficient to trigger the formation of LTP.

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Following reports of epidemiological studies in Greenland in the early 1970s, n-3 polyunsaturated fatty acids （PUFAs） were investigated with high hopes for their preventive effects on atherosclerotic disease and they have now come into clinical use. Subsequently, research interest in n-3 PUFAs expanded into the field of psychiatry. A case-control study conducted in the UK by Fehily et al. in 1981 was likely the first to note the association between n-3 PUFAs and depression, based on findings of reduced blood levels of n-3 PUFAs in patients with endogenous depression compared with age- and sex-matched healthy controls. Then, in 1998 Hibbeln reported an ecological study conducted in 9 countries that found a negative association between fish consumption and the prevalence of depression. This prompted a marked increase in the number of epidemiological studies and clinical trials of n-3 PUFAs. Furthermore, in 2002 Hibbeln reported an ecological study conducted in 22 countries that showed a similar association between fish consumption and the prevalence of postnatal depression, again prompting the acceleration of research—this time in the field of perinatal depression. In this review, I introduce studies on 1） the association between n-3 PUFAs and/or fish consumption and the risk of prenatal and/or postnatal depression, 2） the association between blood levels of n-3 PUFAs and the risk of prenatal and/or postnatal depression, and 3） randomized controlled trials of n-3 PUFAs for prenatal and/or postnatal depression.

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The findings of an epidemiological study of Greenlandic Inuit suggested that fish oil （omega-3 fatty acids） was important in preventing atherosclerotic disease. After its landmark study, many large-scale epidemiological studies, clinical outcomes trials, and meta-analyses have examined the health benefits of omega-3 fatty acids as part of a diet rich in fatty acids. In Japan, the fisherman study at Kawazu, a village of Katsuura city in Chiba prefecture, also demonstrated the omega-3 rich diet contributes the prevention of cardiovascular diseases, and the highly concentrated eicosapentaenoic acid-ethyl ester was developed for the treatment of dyslipidemia. This article reviews studies on omega-3 fatty acids during the last 50 years including the progress of both molecular mechanism and recent large-scale clinical studies.

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Lipid oxidation, a process that has been associated with the deterioration of foods and the pathogenesis of various diseases, forms lipid hydroperoxides as the primary product. Lipid oxidation can happen through different oxidation mechanisms （e.g., singlet oxygen oxidation and free radical oxidation）, and importantly, lipid hydroperoxides that are formed through different oxidation mechanisms differ in their positional and stereoisomeric structures of the hydroperoxide group. Thus, analysis of the detailed structures of lipid hydroperoxides, especially around the hydroperoxide group, enables the estimation of lipid oxidation mechanisms. Recent advances in analytical techniques including our use of sodium ion during MS/MS analysis, have enabled the structural analysis of various lipid hydroperoxides as well as the estimation of oxidation mechanisms. One example is the oxidation of squalene, which is a lipid present in foods and human skin surface lipids. Oxidation of squalene causes a decrease in the nutritional value of foods as well as adverse skin conditions; thus, we recently made approaches towards estimating squalene oxidation mechanisms via structural analysis of squalene monohydroperoxide, the primary oxidation product of squalene. We herein review our recent efforts towards estimation of lipid oxidation mechanisms by structural analysis of lipid hydroperoxides, with focus on squalene oxidation.

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