1. Docosahexaenoic acid (DHA) is a nutritionally essential n-3 polyunsaturated fatty acid (PUFA) that is concentrated in brain synaptic membranes and is thought to be deficient in patients with bipolar disorder and Alzheimer disease. It is important to understand how brain DHA is regulated. In post-weaning rats diet deprived of n-3 PUFAs for 15 weeks, we showed with radiolabeled DHA and kinetic modeling that brain DHA is lost 2-3 fold more slowly than in control diet rats. We are examining how the brain reduces it's rate of DHA loss. (DeMar et al 2004) 2. Alpha-linolenic acid, a n-3 PUFA precursor of docosahexaenoic acid (DHA), does not contribute appreciably to DHA synthesis in brain phospholipids of adult rats fed a diet containing DHA. Attempts to replenish purported low levels of brain DHA in patients with Alzheimer disease or bipolar disorder should add DHA rather than its shorter chain precursors to the diet. (Demar et al 2005) 3. Arachidonic acid (AA) participates in neuroreceptor initiated brain signal transduction. We applied our fatty acid method with PET to quantify atrophy-corrected AA incorporation rates into brain phospholipids of young and elderly healthy human volunteers. We also measured their regional cerebral blood flow with radiolabeled water. Both AA incorporation and blood flow did not differ significantly between the two age groups. Thus, brain energy and lipid metabolism remain intact with healthy human aging (Giovacchini et al 2004) 4. We used our in vivo fatty acid model to image brain arachidonic acid metabolism in an animal model of neuroinflammation (rats in which bacterial lipopolysaccharide was infused into the cerebral ventricles for 6 days). In these rats, arachidonic acid incorporation was elevated in relation to increased brain activities of phospholipase A2 enzymes that release arachidonic acid from membrane phospholipid. These positive results suggest that the fatty acid method can be used to image neuroinflammation diseases like Alzheimer disease, in which postmortem evidences suggest that neuroinflammation occurs. We have published a way to do this with positron emission tomography (PET) and intravenously injected radiolabeled arachidonic acid. (Lee et al 2004; Rosenberger et al 2004)
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