Volume 36, Issue 9 p. 945-959
Article

Mechanisms of action of docosahexaenoic acid in the nervous system

Norman Salem Jr.

Corresponding Author

Norman Salem Jr.

Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 12420 Parklawn Dr., Room 150, Rockville, Marland, 20852

To whom correspondence should be addressed at 12420 Parklawn Dr., Room 150, Rockville, MD 20852. E-mail: [email protected]Search for more papers by this author
Burton Litman

Burton Litman

Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 12420 Parklawn Dr., Room 150, Rockville, Marland, 20852

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Hee-Yong Kim

Hee-Yong Kim

Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 12420 Parklawn Dr., Room 150, Rockville, Marland, 20852

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Klaus Gawrisch

Klaus Gawrisch

Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 12420 Parklawn Dr., Room 150, Rockville, Marland, 20852

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First published: 01 September 2001
Citations: 719

Abtract

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 responance studies to delineate differences in molecular structure and order in biomembranes due to subtle changes in the degree of phospholipid unsaturation.