Our past studies as well as those of others have indicated that alcohol abuse leads to a loss in tissue DHA. Nutritional inadequacies particularly during early development may also lead to such losses in this essential fatty acid. In following up this work, it is important to establish what losses in physiological functions are caused by the loss of DHA in various organ systems. Our recent work has focused upon the nervous system. A novel application to the field of essential fatty acid biology was made with the introduction of olfactory-based learning and memory-related tasks for brain function assessment. This modality was used since Slotnick has reported that rats are capable of high level learning of olfactory based tasks of a nature usually only ascribed to non-human primates or higher mammals. Our principal findings are that there is a poorer performance in the acquisition of olfactory set learning in rats where brain and olfactory bulb DHA was lowered thru dietary insufficiency. That is, after the rats had acquired the task, they were over-trained in order to determine whether they could achieve the learning set, ie., make zero or only one mistake in the first twenty trials after an information trial in a two odor discrimination task. Rats given a safflower oil based diet for two generations were significantly poorer in this regard than rats to which oils containing alpha-linolenate and DHA were added. Spatial maze tasks including the water maze also indicated that animals with lower levels of brain DHA performed more poorly, swimming longer and at a higher rate, but finding the platform with a longer latency. In a retention trial, n-3 deficient rats performed significantly worse than the n-3 adequate group, especially when deprived for three generations. Although n-3 deficient rats perform more poorly, it cannot be ascribed to lower activity or motivation as general motor activity was not different between groups and there was no difference in a progressive-ratio licking task in which animals worked for a water reward. The n-3 deficient rats sampled the odors longer than the DHA-adequate animals but still made more subsequent total errors. The n-3 deficient rats were also examined for changes in brain morphology using quantitative stereological techniques. Initially, studies focused on hippocampal morphology. After fixing and cresyl violet staining, a variety of features were quantified in rats fed the n-3 deficient or adequate diets for three generations. No statistically significant differences were observed in volume, density or total number of perikarayal neurons in the hippocampus. However, perikarayal size in the septal area of the CA1 field of the hippocampus was greater in the n-3 adequate (containing DHA) group relative to the deficient group. An attempt was made to extend aspects of these studies to non-human primates. For the first six months of life, rhesus monkeys were fed either standard infant formula or formula supplemented with AA and DHA. Striking improvements in visual orientation skills and in motor development were found during the first month of life among infants fed supplemented formulas. Physiological differences in neuronal control of the autonomic nervous system persisted into adolescence. This animal work has important implications for human infant formula composition as formulas are currently devoid of DHA in North America thus leading to a decrease in infant brain DHA levels and suboptimal development and function. An effort was begun to develop a method following the work of Junji Hoshiba for auto-rearing of rat pups starting from the first day of life. In this way, it will be possible to control the essential fatty acid composition of the diet throughout the entire life cycle of the rat, an animal which is born at a relatively immature stage relative to primates, and has often been used as a model of fetal development. This model will be used to induce changes in brain DHA composition in the first generation of animals and may therefore provide for a great savings in the use of animals and in the time needed to produce a model of n-3 deficiency. This apparatus will also make possible a new model of fetal alcohol syndrome where animals can be given alcohol from the first days of life. In related work, an effort was made to determine whether changes in essential fatty acids, particularly of the n-3 category, are associated with psychiatric illnesses. Among 200 elderly subjects from rural Iowa, plasma DHA concentrations were lower among depressed women compared to control women. Lower plasma DHA concentrations also predicted greater reports of anxiety and more numerous sleep complaints. Among 11,234 Finnish subjects, reports of infrequent fish consumption predicted more severe scores on the Beck Depression Inventory. Among subjects who recently attempted suicide, low plasma EPA concentrations strongly predicted more severe psychopathology on eight psychiatric rating scales. These scales predict continued risk of suicide. A cross-national comparison of fish consumption and the prevalence of postpartum depression was conducted among 24 countries. Greater fish consumption predicted a lower risk of suffering a postpartum depression. (r= - 0.71, p<0.0005). Higher DHA content of mothers milk also predicted decreased risk of suffering a postpartum depression (r= -0.82, p<0.0006, n=13).
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