Chaired by Norman Salem, NIAAA

Balcony B, Natcher Conference Center

Polyunsaturated fatty acids (PUFAs) have long been recognized as essential nutrients for proper growth and physiological function in mammals.  More recently, the functions of the highly unsaturated PUFAs arachidonic acid (AA) and docosahexaenoic (DHA) acid, have been intensively explored with particular attention to the nervous system where they are highly concentrated.  Dietary restriction of omega-3 fatty acids leads to decreased brain and retinal levels of DHA and an impairment in spatial task performance, olfactory discrimination and set learning and may alter the emotional state so as to increase the effects of stress.  A series of in vivo studies in the mammalian retina as well as in vitro reconstitution experiments demonstrate that DHA-containing phospholipids are required for optimal speed and efficiency of G protein-coupled signaling in the retina outer segment.  The relationship of PUFAs with various bioactivators including eicosanoids, angiogenic factors, neuromodulators, cytokines and bioactive compounds in the context of basic and clinical research on three blinding retinal diseases of public health significance will be discussed.  People reporting the highest dietary intakes of long chain omega-3 fatty acids were less likely to have neovascular age-related macular degeneration (AMD) and vision loss.  A rat model of neuroinflammation will be presented involving LPS infusion that leads to elevated brain activities of phospholipase A2 enzymes that are coupled to cytokine and NMDA receptors, elevated release of AA from brain phospholipid, and increased conversion of AA to PGE2 and other eicosanoids.  The elevated AA metabolic loss could be imaged in awake rats using quantitative autoradiography and in Alzheimer’s patients using PET where an increased AA incorporation was observed in brain regions in which blood flow was reduced.  Taken together, these studies suggest that the increased incorporation in the patients represented an upregulated AA cascade, and that this aspect of neuroinflammation can be imaged in human brain disorders.  Thus, this symposium will provide an interdisciplinary insight into highly unsaturated lipid function that will span the spectrum of from clinical studies to membrane biophysics and from behavior to biochemistry.

Program:

Docosahexaenoic Acid:  An Essential Nutrient for Optimal Brain Function
Norman Salem, NIAAA

In Vivo Arachidonic Acid Imaging in a Rat Model of Neuroinflammation and in Alzheimer’s Disease Patients
Stanley Rapoport, NIA

The Role of Polyunsaturated Lipids in Health and Disease of the Retina
John Paul San Giovanni, NEI

Polyunsaturated Phospholipid Regulation of GPCR Signaling
Drake Mitchell, NIAAA