[PDF] Mechanisms of action of docosahexaenoic acid in the nervous system | Semantic Scholar (2024)

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.

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.

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.

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.

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.

...

...

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.

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.

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.

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.

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.

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).

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 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.

...

...