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      Dietary (n-3) Fatty Acids and Brain Development

      The Journal of Nutrition
      Oxford University Press (OUP)

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          Abstract

          The (n-3) fatty acids are essential dietary nutrients, and one of their important roles is providing docosahexaenoic acid [22:6(n-3)] (DHA) for growth and function of nervous tissue. Reduced DHA is associated with impairments in cognitive and behavioral performance, effects which are particularly important during brain development. Recent studies suggest that DHA functions in neurogenesis, neurotransmission, and protection against oxidative stress. These functions relate to the roles of DHA within the hydrophobic core of neural membranes and effects of unesterified DHA. Reviewed here are some of the recent studies that have begun to elucidate the role of DHA in brain development and function. A better understanding of development and age-specific changes in DHA transfer and function in the developing brain may provide important insight into the role of DHA in developmental disorders in infants and children, as well as at other stages of the lifespan.

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          Most cited references60

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          Mechanisms of action of docosahexaenoic acid in the nervous system.

          This review describes (from both the animal and human literature) the biological consequences of losses in nervous system docosahexaenoate (DHA). It then concentrates on biological mechanisms that may serve to explain changes in brain and retinal function. Brief consideration is given to actions of DHA as a nonesterified fatty acid and as a docosanoid or other bioactive molecule. The role of DHA-phospholipids in regulating G-protein signaling is presented in the context of studies with rhodopsin. It is clear that the visual pigment responds to the degree of unsaturation of the membrane lipids. At the cell biological level, DHA is shown to have a protective role in a cell culture model of apoptosis in relation to its effects in increasing cellular phosphatidylserine (PS); also, the loss of DHA leads to a loss in PS. Thus, through its effects on PS, DHA may play an important role in the regulation of cell signaling and in cell proliferation. Finally, progress has been made recently in nuclear magnetic resonance studies to delineate differences in molecular structure and order in biomembranes due to subtle changes in the degree of phospholipid unsaturation.
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            Omega-3 fatty acids and monoamine neurotransmission.

            We proposed several years ago that the behavioral effects of n-3 PUFA deficiency observed in animal models might be mediated through the dopaminergic and serotonergic systems that are very involved in the modulation of attention, motivation and emotion. We evaluated this hypothesis in an extended series of experiments on rats chronically diet-deficient in alpha-linolenic acid, the precursor of long-chain n-3 PUFA, in which we studied several parameters of these neurotransmission systems. The present paper synthesizes the main data we obtained on interactions between n-3 PUFA status and neurotransmission in animal models. We demonstrated that several parameters of neurotransmission were affected, such as the vesicular pool of dopamine and serotonin, thus inducing several regulatory processes such as modification of cerebral receptors in specific brain areas. We also demonstrated that (i) a reversal diet with adequate n-6 and n-3 PUFA given during the lactating period to rats originating from alpha-linolenic acid-deficient dams was able to restore both the fatty acid composition of brain membranes and several parameters of the dopaminergic and serotonergic neurotransmission, and (ii) when given from weaning, this reversal diet allowed partial recovery of biochemical parameters, but no recovery of neurochemical factors. The occurrence of profound n-3 PUFA deficiency during the lactating period could therefore be an environmental insult leading to irreversible damage to specific brain functions. Strong evidence is now showing that a profound n-3 PUFA experimental deficiency is able to alter several neurotransmission systems, at least the dopaminergic and serotonergic. Whether these experimental findings can be transposed to human pathophysiology must be taken cautiously, but reinforces the hypothesis that strong links exist between the PUFA status, aspects of brain function such as neurotransmission processes and behavior.
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              Docosahexaenoic acid promotes neurogenesis in vitro and in vivo.

              Docosahexaenoic acid (22:6n-3), one of the main structural lipids in the mammalian brain, plays crucial roles in the development and function of brain neurons. We examined the effect of docosahexaenoic acid on neuronal differentiation of neural stem cells in vitro and in vivo. Neural stem cells obtained from 15.5-day-old rat embryos were propagated as neurospheres and cultured under differential conditions with or without docosahexaenoic acid for 4 and 7 days. Docosahexaenoic acid significantly increased the number of Tuj1-positive neurons compared with the control on both culture days, and the newborn neurons in the docosahexaenoic acid group were morphologically more mature than in the control. Docosahexaenoic acid significantly decreased the incorporation ratio of 5-bromo-2'-deoxyuridine, the mitotic division marker, during the first 24 h period; it also significantly decreased the number of pyknotic cells on day 7. Thus, docosahexaenoic acid promotes the differentiation of neural stem cells into neurons by promoting cell cycle exit and suppressing cell death. Furthermore, dietary administration of docosahexaenoic acid significantly increased the number of 5-bromo-2'-deoxyuridine(+)/NeuN(+) newborn neurons in the granule cell layer of the dentate gyrus in adult rats. These results demonstrate that docosahexaenoic acid effectively promotes neurogenesis both in vitro and in vivo, suggesting that it has the new property of modulating hippocampal function regulated by neurogenesis.
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                Author and article information

                Journal
                The Journal of Nutrition
                Oxford University Press (OUP)
                0022-3166
                1541-6100
                April 2007
                April 01 2007
                April 2007
                April 01 2007
                : 137
                : 4
                : 855-859
                Article
                10.1093/jn/137.4.855
                17374644
                abf3063b-7f30-415f-85eb-75c643760d77
                © 2007
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