Mechanisms of action of docosahexaenoic acid in the nervous system

  title={Mechanisms of action of docosahexaenoic acid in the nervous system},
  author={Norman Salem and Burton J. Litman and Hee-Yong Kim and Klaus Gawrisch},
AbtractThis 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… 
[The role of docosahexaenoic acid in neuronal function].
The results of high DHA content in neuronal membranes and formation of DHA derivates, as well as the function of D HA-dependent phosphatidylserine, may explain the promising results supporting beneficial DHA supplementation in neurodegenerative diseases and improvement of brain function.
Biochemical and biological functions of docosahexaenoic acid in the nervous system: modulation by ethanol.
  • Hee-Yong Kim
  • Biology, Medicine
    Chemistry and physics of lipids
  • 2008
Molecular and Signaling Mechanisms for Docosahexaenoic Acid-Derived Neurodevelopment and Neuroprotection
The DHA status in the brain influences not only the PS-dependent signal transduction but also the metabolite formation and expression of pre- and post-synaptic proteins that are downstream of the CREB and affect neurotransmission.
Docosahexaenoic acid,22:6n-3: Its roles in the structure and function of the brain
Effects of docosapentaenoic acid on neuronal apoptosis
The data suggest that depletion of DHA from neuronal tissues may have a compounding effect on Raf-1 translocation in growth factor signaling and the fact that DPA cannot fully support the protective role played by DHA may provide a basis for the adverse effect of n−3 FA deficiency on neuronal development and function.
Novel Metabolism of Docosahexaenoic Acid in Neural Cells*
In this review, biochemical mechanisms for enriching and metabolizing DHA in neural cells are discussed in the context of their biological significance in neuronal function.
Docosahexaenoic acid affects cell signaling by altering lipid rafts.
The uptake of DHA into brain phosphatidylethanolamines and the subsequent exclusion of cholesterol from the DHA-rich membranes is reported and a proposal of how DHA incorporation into membranes may control cell biochemistry and physiology is proposed.


Reversal of docosahexaenoic acid deficiency in the rat brain, retina, liver, and serum.
A consideration of the total amounts and time courses of DHA repleted in the nervous system compared with the liver and circulation suggests that transport-related processes may limit the rate of D HA repletion in the retina and brain.
Apoptosis of Retinal Photoreceptors During Development In Vitro: Protective Effect of Docosahexaenoic Acid
It is shown that, unlike other retinal neurons, photoreceptors die through an apoptotic pathway, and DHA was the most effective in promoting photoreceptor survival, and the only one to decrease the number of apoptotic nuclei.
Effect of Docosahexaenoic Acid on the Synthesis of Phosphatidylserine in Rat Brain Microsomes and C6 Glioma Cells
The data show that neuronal and glial PS synthesis is sensitive to changes in the docosahexaenoate levels of phospholipids and suggest that 22:6n‐3 may be a modulator of PS synthesis, while C6 glioma cells cultured for 24 h in 22:3‐3‐Supplemented media showed a significant increase in the synthesis of [3H]PS when compared with unsupplemented cells.
Dietary supplementation with eicosapentaenoic and docosahexaenoic acid inhibits growth of Morris hepatocarcinoma 3924A in rats: Effects on proliferation and apoptosis
The anti‐tumoral effect of EPA is related mainly to its inhibition of cell proliferation, whereas that of DHA corresponds with its induction of apoptosis, and alterations in fatty‐acid composition induced by EPA or DHA appear to be factors underlying their differential actions on cell proliferation and apoptosis.
Inhibition of Neuronal Apoptosis by Docosahexaenoic Acid (22:6n-3)
Collectively, enrichment of neuronal cells with 22:6n-3 increases the PS content and Raf-1 translocation, down-regulates caspase-3 activity, and prevents apoptotic cell death, strongly suggesting that the protective effect of 22: 6n- 3 may be mediated at least in part through the promoted accumulation of PS in neuronal membranes.
Cerebral endothelium and astrocytes cooperate in supplying docosahexaenoic acid to neurons.
  • S. Moore
  • Biology
    Advances in experimental medicine and biology
  • 1993
The present studies and previously published work support a model for supplying DHA to central nervous system neurons that could utilize either DHA or its omega-3 fatty acid precursors circulating in the blood (Figure 4).
n−3 Fatty acid deficiency decreases phosphatidylserine accumulation selectively in neuronal tissues
Results establish that variations in membrane 22∶6n−3 fatty acid composition have a profound influence on PS accumulation in neuronal tissues where 22∵6n −3 is abundant and have implications in neuronal signaling events where PS is believed to play an important role.
The release of polyunsaturated fatty acids and their lipoxygenation in the brain.
The results suggest that 22:6n3 may be of more physiological importance in neuronal membranes as a membrane component rather than as a released free fatty acid while in astroglia, release of 22:4n6 may also be a significant step involved in receptor-stimulated signaling processes.