Mechanism of omega-6 and omega-3 fatty acid transport across the blood brain barrier

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Fatty acids (FAs) are important to both the developing and mature central nervous system. While the brain can make some fatty acids, there are a number of polyunsaturated fatty acids (PUFAs) including linoleic acid (LA) and alpha linolenic acid (ALA) that must be obtained through the diet. In addition, the brain has a limited ability to make key essential omega-6 and omega-3 PUFAs such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). These essential fatty acids are absorbed into the bloodstream and enter the brain through brain microvessel endothelial cells that form the blood-brain barrier (BBB). In addition, how proinflammatory FAs such as arachidonic acid (AA) enter into the brain and alter brain function is unknown. The proposed research will examine how FA transport across the BBB occurs with a focus on the PUFAs which are primarily obtained through the diet and on AA, a known proinflammatory FA. Our hypothesis is that the essential PUFAs, ALA, EPA and DHA undergo transport across the BBB through specific fatty acid transport proteins expressed in the brain microvessel endothelial cells and that AA may dramatically alter not only BBB FA transport but also other membrane transport properties. The objectives of the proposal are to: 1. Determine the mechanisms for transport of omega-6 and omega-3 fatty acids across the BBB., 2. Examine the cellular processing of these FAs in the brain microvasculature., 3. Evaluate the effects of both short-term (i.e. 2-60 min) and long-term (i.e. 24-48 h) exposure of FAs on BBB function. The proposed studies will provide important information concerning the mechanisms involved in PUFA transport and distribution in the brain and the effects of PUFAs on BBB function. Given the evidence concerning the vital importance of PUFA in human brain function, the proposed studies are fundamental to the application of various PUFA in the development of the brain and the treatment of central nervous system related diseases such as Alzheimer's disease , depression, schizophrenia, attention deficit and hyperactivity disorders.