Polyunsaturated fatty acids and their metabolites in brain function and disease

The brain is especially enriched with the two polyunsaturated fatty acids arachidonic acid and docosahexaenoic acid. Although, quantitatively speaking, they are primarily esterified to brain phophospholipids, they can be released from the membrane and transformed into highly biologically active molecules.The mechanisms by which the brain takes up polyunsaturated fatty acids are not clear and remain controversial. Candidate plasma pools include phospholipids as part of lipoproteins, unesterified fatty acids and lysophospholipids. Because polyunsaturated fatty acids are derived from the diet, changes in their intakes can alter brain levels and thus the activity of pathways regulated by polyunsaturated fatty acids in the brain.In response to neuroreceptor activation, fatty acids are released from the membrane and participate in cell signalling.So far, polyunsaturated fatty acids and their biologically active derivatives have been shown to regulate cell survival, neurogenesis, brain inflammation and synaptic function.Altered fatty acid signalling has been implicated in mood disorders, cognition, Alzheimer's disease, schizophrenia and other conditions. Research using animal models has shown promise in targeting brain polyunsaturated fatty acid metabolism with diet or drugs; however, translational studies often do not yield statistically significant results. New methods to target brain polyunsaturated metabolism are emerging as novel approaches to treat brain disorders.