| Biography: Dr. Rapoport received his M.D. from Harvard Medical School, Boston, interned in Medicine at Bellevue Hospital, New York, and received post-doctoral training at the Department of Physiology, University of Uppsala, Sweden, and at the Laboratory of Neurophysiology, National Institute of Mental Health (NIMH). He was appointed as a tenured scientist at NIMH in 1968, and 1978-1999 was Chief of the Laboratory of Neurosciences, NIA. He currently is Chief of the Section on Brain Physiology and Metabolism, NIA. He is a Fellow of the American College of Neuropsychopharmacology, the American Academy of Neurology and the Gerontological Society of America. |
| Brain Phospholipid Metabolism in Relation to Signal Transduction and Neuroplasticity: Phospholipids are major constituents of cell membranes and participate in neuroplastic remodeling and signal transduction. We developed in rats an in vivo method and model to localize and quantify brain phospholipid metabolism and turnover of fatty acids within specific sites of brain phospholipids. A radiolabeled long chain fatty acid (unsaturated arachidonate or docosahexaenoate, saturated palmitate) is injected intravenously and its rate of incorporation into brain is measured using quantitative autoradiography and chemical analysis. With this model, we showed that lithium, used clinically to treat manic depressive disorder, reduces arachidonate turnover by some 80% without affecting turnover of docosahexaenoate and palmitate, and thus likely acts on phospholipase A2. Additionally, C11-labeled fatty acids were synthesized, in collaboration with the PET Department at NIH, and are used to image phospholipid metabolism of monkey brain with PET (tracer uptake was independent of blood flow) and to initiate a clinical PET protocol on healthy controls at rest and during activation. We plan to extend this protocol and related animal protocols to image phospholipase A2-mediated signal transduction involving the brain, cholinergic, serotoninergic and dopaminergic systems. |
- Rosenberger TA, Villacreses NE, Hovda JT, Bosetti F, Weerasinghe G, Wine RN, Harry GJ, Rapoport SI. Rat brain arachidonic acid metabolism is increased by a 6-day intracerebral ventricular infusion of bacterial lipopolysaccharide. J Neurochem. 88(5): 1168-1178, 2004.
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- Teipel SJ, Alexander GE, Schapiro MB, Moller HJ, Rapoport SI, Hampel H. Age-related cortical grey matter reductions in non-demented Down's syndrome adults determined by MRI with voxel-based morphometry. Brain.127(Pt 4): 811-824, 2004.
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- Rapoport SI. Coupled reductions in brain oxidative phosphorylation and synaptic function can be quantified and staged in the course of Alzheimer disease. Neurotox Res. 5(6): 385-398, 2003.
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- Bosetti F, Weerasinghe GR, Rosenberger TA, Rapoport SI. Valproic acid down-regulates the conversion of arachidonic acid to eicosanoids via cyclooxygenase-1 and -2 in rat brain. J Neurochem. 85(3): 690-696, 2003.
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- Rosenberger TA, Villacreses NE, Contreras MA, Bonventre JV, Rapoport SI. Brain lipid metabolism in the cPLA2 knockout mouse. J Lipid Res. 44(1): 109-117, 2003.
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- Giovacchini G, Chang MC, Channing MA, Toczek M, Mason A, Bokde AL, Connolly C, Vuong BK, Ma Y, Der MG, Doudet DJ, Herscovitch P, Eckelman WC, Rapoport SI, Carson RE. Brain incorporation of [11C]arachidonic acid in young healthy humans measured with positron emission tomography. J Cereb Blood Flow Metab. 22(12): 1453-1462, 2002.
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- Rapoport SI, Bosetti F. Do lithium and anticonvulsants target the brain arachidonic acid cascade in bipolar disorder? Arch Gen Psychiatry. 59(7): 592-596, 2002.
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- Contreras MA, Rapoport SI. Recent studies on interactions between n-3 and n-6 polyunsaturated fatty acids in brain and other tissues. Curr Opin Lipidol.13(3): 267-272, 2002.
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