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Keywords:

Alzheimers disease, multiple sclerosis, cerebral ischemia, spinal cord injury, AIDS-related dementia, neurodegeneration, neuroinflammation, brain, lipid metabolism, lipid-mediated signal transduction, fatty acid metabolism, phospholipid metabolism, arachidonic acid, eicosanoids, ether phospholipid, plasmalogens, phospholipases A₂, phospholipases C, analytical lipid techniques

Education/Training:

• Postdoctoral Fellow, National Institutes on Aging, National Institutes of Health, Bethesda, Maryland
• Ph.D., Medical Biochemistry, The Ohio State University, Columbus, Ohio

Research Interest:

Inflammation induced tissue injury is a major and primary contributing factor to the pathogenesis of a variety of human brain diseases including; cerebral ischemia, spinal cord injury, multiple sclerosis, AIDS-related dementia, and Alzheimers disease. Inflammation induces the production, by activated microglia and astrocytes, of the pro-inflammatory cytokines (e.g. IL-1, TNFa, etc.). These cytokines bind to receptors that, among other things, couple to “effector” enzymes such as phospholipases A₂ and phospholipases C, provoking pathological lipid-mediated signaling cascades. Induction of these cascades is known to disrupt membrane phospholipid metabolism, increase the expression of enzymes found in the inflammatory cascades, and ultimately result in altered cellular homeostasis and cell death. Unfortunately, little is known concerning the relative contribution that specific inflammation-induced signaling pathways play in the progression of neurodegenerative events associated with these diseases.

Our long-term goal is to understand the extent by which alterations in lipid-mediated signal transduction contribute to the progression of injury associated with neuroinflammation and to use this knowledge to develop therapeutic strategies to treat these diseases. Studies in our laboratory include: identifying lipid-mediated signaling pathways that contribute to the progression of inflammatory events in the central nervous system, identifying the specific roles phospholipases A₂ and C play in the progression of disease, and to distinguish the role that ether phospholipid metabolism has in normal and injured brain.

Refereed Publications:

• Rosenberger, T.A., Farooqui, A.A., and Horrocks, L.A. (2007) Bovine Brain Diacylglycerol Lipase: Substrate Specificity and Activation by Cyclic AMP-dependent Protein Kinase Lipids 42, 187-95.
• Golovko, M.Y., Rosenberger, T.A., Fedderson, S., Færgeman, N.J., and Murphy, E.J. (2007) a-Synuclein gene-ablation increases docosahexaenoic acid incorporation and turnover in brain phospholipids J. Neurochem. 101, 201-211.
• Ma, K, Deutsch, J, Villacreses, N.E., Rosenberger, T.A., Rapoport, S.I., and Shetty, U. (2006) Measuring brain uptake and incorporation into brain phosphatidylinositol of plasma myo-[²H₆]inositol in unanesthetized rats: An approach to estimate in vivo brain phosphatidylinositol turnover. Neurochem. Res. 31, 759-765.
• Golovko, M.Y., Rosenberger, T.A., Faergeman, N.J., Seddersen, S., Cole, N.B., Pribill, I., Berger, J., Nussbaum, R.L., and Murphy, E.J. (2006) Acyl-CoA synthetase activity links wild-type but not mutant a-synuclein to brain arachidonate metabolism. Biochemistry. 45, 6956-6966.
• Bazinet RP, Weis MT, Rapoport SI, Rosenberger TA. (2006) Valproic acid selectively inhibits conversion of arachidonic acid to arachidonoyl-CoA by brain microsomal long-chain fatty acyl-CoA synthetases: relevance to bipolar disorder. Psychopharmacology 184(1):122-9.
• Bazinet, R.P., Lee, H., Felder, C.C., Porter, A.C., Rapoport, S.I., and Rosenberger, T.A. (2005) Rapid high-energy microwave fixation is required to determine the anandamide (N-arachidonoylethanolamine) concentration of rat brain. Neurochem. Res. 30: 597-601.
• Patrick, C.B., McHowat, J., Rosenberger, T.A., Rapoport, S.I., and Murphy, E.J. (2005) Arachidonic acid incorporation and turnover is decreased in sympathetically denervated rat heart. Amer. J. Physiol. Heart Circ. Physiol. 288: H2611-H2619.
• Lee, H., Villacreses, N.E., Rapoport, S.I., and Rosenberger, T.A. (2004) In vivo imaging detects a transient increase in brain arachidonic acid metabolism: A potential marker of neuroinflammation. J. Neurochem. 91: 936-945.
• Rosenberger, T.A., Villacreses, N.E., Hovda, J.T., Bosetti, F., Weerasinghe, G., Wine, R.N., Harry, G.J., and Rapoport, S.I. (2004) Rat brain arachidonic acid metabolism is increased by a 6-day intracerebral ventricular infusion of bacterial lipopolysaccharide. J. Neurochem. 88: 1168-1178.
• Bosetti, F., Weerasinghe, G., Rosenberger, T.A., and Rapoport, S.I. (2003) Valproic acid down-regulates the conversion of arachidonic acid to eicosanoids via cyclooxygenase-1 and -2 in rat brain. J. Neurochem. 85: 690-696.
• Rosenberger, T.A., Villacreses, N.E., Contreras, M.A., Bonventre, J.V., and Rapoport, S.I. (2003) Altered brain lipid metabolism in the cytosolic phospholipase A₂ (cPLA₂) knockout mouse. J. Lipid Res. 44: 109-117.
• Deutsch, J., Rapoport, S.I., and Rosenberger, T.A. (2003) Valproyl-CoA and esterified valproate are not found in brains of rats treated with valproic acid, but the brain concentrations of CoA and acetyl-CoA are altered. Neurochem. Res. 28: 861-866.
• Rosenberger, T.A., Hovda, J.T., and Peters, J.M. (2002) Targeted disruption of the nuclear hormone receptor, PPARb (d), results in distinct gender differences in mouse brain phospholipid and esterified FA levels. Lipids 37: 495-500.
• Purdon, A.D., Rosenberger, T.A., Shetty, H.U., and Rapoport, S.I., (2002) Energy consumption by phospholipid metabolism in mammalian brain. Neurochem. Res. 27: 1641-1647.
• Rosenberger, T.A., Oki, J., Purdon, A.D., Rapoport, S.I., and Murphy, E.J. (2002) Rapid synthesis and turnover of brain microsomal ether phospholipids in the adult rat. J. Lipid Res. 43: 59-68.
• Bosetti, F., Rintala, J., Seemann, R., Rosenberger, T.A., Contreras, M.A., Rapoport, S.I., and Chang, M.C.J. (2002) Chronic lithium downregulates cyclooxygenase-2 activity and prostaglandin E₂ concentration in rat brain. Mol. Psychiatry. 7: 845-850.
• Deutsch, J., Rapoport, S.I., and Rosenberger, T.A. (2002) Coenzyme A and short-chain acyl-CoA species in control and ischemic rat brain. Neurochem. Res. 27: 1577-1582.
• Contreras, M.A., Chang, M.C.J., Rosenberger, T.A., Sheaff-Greiner, R., Myers, C.S., Salem, N., and Rapoport, S.I. (2001) Chronic nutritional deprivation of n-3 a-linolenic acid does not affect n-6 arachidonic acid recycling within brain phospholipids of awake rats J. Neurochem. 79: 1090-1099.
• Chang, M.C.J., Contreras, M.A., Rosenberger, T.A., Rintala, J., Bell, J.M., and Rapoport, S.I. (2001) Chronic valproate treatment decreases the in vivo turnover of arachidonic acid in brain phospholipids: A possible common effect of mood stabilizers. J. Neurochem. 77: 796-803.
• Murphy, E.J., Rosenberger, T.A., Patrick, C.B., and Rapoport, S.I. (2000) Arachidonic acid targets phospholipids and palmitate targets neutral lipids in hearts of awake rats. Lipids 35: 891-898.
• Rintala, J., Seemann, R., Chandrasekaran, K., Rosenberger, T.A., Chang, L., Contreras, M., Rapoport, S.I., and Chang, M.C.J. (1999) A 85 kDa cytosolic phospholipase A₂ is a target for chronic lithium in rat brain. NeuroReport 10: 3887-3890.
• Farooqui, A.A., Yang, H.C., Rosenberger, T.A., and Horrocks, L.A. (1997) Phospholipase A₂ and its role in brain tissue. J. Neurochem. 69: 889-901.
• Murphy, E.J., Rosenberger, T.A., and Horrocks, L.A. (1997) Effects of maturation on the phospholipid and phospholipid fatty acid compositions in primary rat cortical astrocytes cell cultures. Neurochem. Res. 22: 1205-1213.
• Murphy, E.J., Rosenberger, T.A., and Horrocks, L.A. (1996) Separation of neutral lipids by high-performance liquid chromatography: quantification by ultraviolet, light scattering and fluorescence detection. J. Chromatogr. B Biomed. Appl. 685: 9-14.
• Murphy, E.J., Haun, S.E., Rosenberger, T.A., and Horrocks, L.A. (1995) Altered lipid metabolism in the presence and absence of extracellular Ca²⁺ during combined oxygen-glucose deprivation in primary astrocyte cultures. J. Neurosci. Res. 42: 109-116.
• Murphy, E.J., Slivka, A.P., Rosenberger, T.A., and Horrocks, L.A. (1993) High-performance liquid chromatography separation and quantitation of methylprednisolone from rat brain. Anal. Biochem. 209: 339-342.

Non-refereed Publications:

• Deutsch, J., and Rosenberger, T.A. (2005) HPLC analysis of acyl-coenzyme A esters from mammalian tissue, in HPLC of Acyl Lipids (Lin, J. and McKeon, T.A. editors) HNB Publishing, New York 499-520.
• Farooqui, A.A., Rosenberger, T.A., and Horrocks, L.A. (1997) Arachidonic acid, neurotrauma and neurodegenerative diseases, in Fatty Acids: Biochemistry and Behavior, (Mostofsky, D.I. and Yehuda, S. editors) Humana Press, Totowa, 277-295.