Roundtable discussion of session 4: fatty acids and lipids in brain disorders.

Discussant_s Remarks (Renee LeBoeuf, University of Washington): I do have one burning question I have to get out of my system, and I think it would be to Dr. Moser. In the X-ALD (X-linked adrenoleukodystrophy) males, 50% have the inflammatory brain version. Is there an association with MHC class molecules like you find in diabetes? (Hugo Moser, Kennedy Krieger Institute): No, there is not. Dr. Kirby Smith and I did that, and it is not. (Arthur Spector, University of Iowa): This is a question for Nick Bazan. I didn’t understand—is the neuroprotective docosanoid present all the time or only in response to injury? The second question is if 15-lipoxygenase is involved in the pathway, arachidonic acid is a very good substrate for it. The PLA2 mechanism should release arachidonate, so are you seeing any arachidonate products of either 15-HETE or something else that might indicate whether arachidonate is being used by that pathway? (Nicolas Bazan, Louisiana State University): Thank you Art, great questions. In fact, we are very astonished by the observation that we cannot detect neuroprotectin-D1 in unstimulated cells. In mouse brain as well as in rat brain, without injury or stimulation, you have no neuroprotectinD1 as well as in all the cells that we have studied up to now. As soon as some sort of stimulation—and the same is true now with the growth factors in our growth factor experiments—as soon as you treat the system, you start to see the accumulation. Insofar as the enzymes involved, we do not know. We feel it is a fit because of the chemical structure. We feel it is a 15-like lipoxygenase. We have not explored this, and you just mentioned a very good experiment to do in parallel, the assays under the same conditions to see if there would be arachidonic acid metabolism. We have not done that yet. But the other issue might be compartmentalization. You see, we were very surprised. The first paper on the release of these two fatty acids measured by mass was in 1970, and we were very surprised that arachidonic acid will go up in the brain very rapidly and DHA will also go up rapidly but will follow a different time kinetics. We are talking about minutes of differences, but the time kinetics are different, that would be in the BBA (Biochimica Et Biophysica Acta) 1970 paper (Bazan 1970) and then the others have confirmed the same kinetics. That is where we are on those issues. (Norman Salem, National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism [NIH/NIAAA]): Nicolas, that was an awesome series of experiments, congratulations. There have been two or three publications which I think you are aware of showing that preloading the diet with fish oil or DHA in animal studies helped mitigate against damage to the brain from ischemia, stroke, or experimentally-induced occlusion of the arteries and so on. Your research suggests another possibility, and now there may be a third. When this challenge is given after the preloading of DHA, is there a difference in the neuroprotectinDl? It’s a little bit hypothetical and I don’t know if you have anything to say. (Bazan): Well, it’s a great question and we are doing things along those lines to try to see if there is a correlation. Again, I believe through the data that we are generating that these are very potent metabolites. I don’t want to call them J Mol Neurosci (2007) 33:120–124 DOI 10.1007/s12031-007-0054-z