Thad A. Rosenberger

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 and acyl-CoA metabolism 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:

Chevalier, A.C. and Rosenberger, T.A. (2017) Increasing acetyl-CoA metabolism attenuates injury and alters spinal cord lipid content in mice subjected to experimental autoimmune encephalomyelitis, J. Neurochem. 141: 721-737.

Zacek, P., Bukowski, M., Rosenberger, T.A., and Picklo, M. (2016) Quantitation of isobaric phosphatidylcholine species in human plasma using a hybrid quadrupole linear trap mass spectrometer, J. Lipid Res. 57: 225-234.

Raatz, S.K., Johnson, L.K., Rosenberger, T.A., and Picklo, M.J. (2016) Dose-dependent intake of farmed Atlantic salmon (Salmo salar) positively influences lipoprotein concentration and particle size in overweight men and women, Nutrition Res, 36: 899-906.

Qin, W., Raatz, S.K., Zhang, K.K., Rosenberger, T.A., and Sauter, E.R. (2014) Polyunsaturated fatty acid content may be increased in the milk of women with pregnancy associated breast cancer, J. Human Lactation 30: 420-424.

Smith, M.D., Bhatt, D.P., Geiger, J.D., and Rosenberger, T.A. (2014) Acetate supplementation modulates brain adenosine metabolizing enzymes and adenosine A2A receptor levels in rats subjected to neuroinflammation, J. Neuroinflammation, 11: 99.

Gienger, H.M., Larson, J., Watt, J.A., and Rosenberger, T.A. (2014) Bacterial lipopolysaccharide induces a dose-dependent activation of neuroglia and loss of basal forebrain cholinergic cells in the rat brain, Inflammation and Cell Signaling 1: 1-9.

Bhatt, D.P. and Rosenberger, T.A. (2014) Acetate treatment increases fatty acid content in LPS-stimulated BV2 microglia, Lipids 49: 621-631.

Rosenberger, T.A. (2014) Editorial Highlight: Targeting calpain-mediated proteolysis and peptide signaling as a strategy to reduce injury in multiple sclerosis, J. Neurochem. 130: 161-164.

Soliman, M.L. and Rosenberger, T.A. (2013) Invited Review: Dietary acetate supplementation attenuates neuroinflammation, Adv. Neuroimmune Biol. 4: 125-140.

Soliman, M.L., Ohms, J.E., and Rosenberger, T.A. (2013) Acetate reduces PGE2 release and modulates phospholipase and cyclooxygenase levels in neuroglia stimulated with lipopolysaccharide, Lipids 48: 651-662.

Soliman, M.L., Combs, C.K., and Rosenberger, T.A. (2013) Modulation of inflammatory cytokines and mitogen-activated protein kinases by acetate in primary astrocytes, J. Neuroimmune Pharm. 8: 287-300.

Bhatt, D.P., Houdek, H.M., Watt, J.A., and Rosenberger, T.A. (2013) Acetate supplementation increases brain phosphocreatine and reduces AMP levels with no effect on mitochondrial biogenesis, Neurochem. Int. 62: 296-305.

Raatz, S.K., Rosenberger, T.A., Johnson, L.K., Wolters, W.W., and Picklo, M.J. Sr. (2013) Dose-dependent consumption of farmed Atlantic salmon (Salmo salar) increases plasma phospholipid n-3 fatty acid differentially, J. Acad. Nutrition and Dietetics 131: 282-287.

Brissette, C.A., Houdek, H.M., Floden, A., and Rosenberger, T.A. (2012) Acetate supplementation reduces microglia activation and brain IL-1β levels in a rat model of Lyme neuroborreliosis, J. Neuroinflammation 9: 249.

Soliman, M.L., Puig, K.L., Combs, C.K., and Rosenberger, T.A. (2012) Acetate reduces microglia inflammatory signaling in vitro, J. Neurochem. 123: 555-567.

Hui, L., Chen, X., Bhatt, D., Geiger, N.H., Rosenberger, T.A., Haughey, N.J., Masino, S.A., and Geiger, J.D. (2012) Ketone bodies protect against HIV-1 Tat-induced neurotoxicity, J. Neurochem. 122: 382-391.

Soliman, M.L., Smith, M.D., Houdek, H.M., and Rosenberger, T.A. (2012) Acetate supplementation modulates brain histone acetylation and decreases IL-1β expression in a rat model of neuroinflammation, J. Neuroinflammation 9: 51.

Bhatt, D.P. Chen, X., Geiger, J.D., and Rosenberger, T.A. (2012) A sensitive HPLC-based method to quantify adenine nucleotides in primary astrocyte cell cultures, J. Chromatography B, Biomed Appl. 889-890: 110-115.

Kakani, R., Fowler, J., Haq, A., Murphy, E.J., Rosenberger, T.A., Berhow, M. and Bailey, C.A. (2012) Camelina meal increases egg n-3 fatty acid content without altering quality or production, Lipids 47: 519-526.

Raatz, S.K., Golovko, M.Y., Brose, S.A., Rosenberger, T.A., Burr, G.S., Wolters, W.R., and Picklo, M.J. (2011) Cooking Reduces Prostaglandin, Resolvin, and Hydroxy-Fatty Acid Content of Farm-Raised Atlantic Salmon, J. Agric. Food Chem. 59: 11278-11286.

Soliman, M.L. and Rosenberger, T.A. (2011) Acetate supplementation increases brain histone acetylation and inhibits histone deacetylase activity and expression, Mol. Cell. Biochem. 352: 173-180.

Reisenauer, C.J., Bhatt, D.P., Mitteness, D.J., Slanczka, E.R., Gienger, H.M., Watt, J.A., and Rosenberger, T.A. (2011) Acetate supplementation attenuates lipopolysaccharide-induced neuroinflammation, J. Neurochem. 117: 264-274.

Rosenberger, T.A., Villacreses, N.E., Weis, M.T., and Rapoport, S.I. (2010) Rat brain docosahexaenoic acid metabolism is not altered by a 6 day intracerebral ventricular infusion of bacterial lipopolysaccharide, Neurochem. Int. 56: 501-507.

Long, E.K., Rosenberger, T.A., and Picklo, M.J. (2010) Ethanol withdrawal increases glutathione adducts of 4-hydroxy-2-hexenal but not 4-hydroxy-2-nonenal in the cerebral cortex, Free Radical Biol. and Med. 48: 384-390.

Frieler, R.A., Mitteness, D.J., Golovko, M.Y., Gienger, H.M., and Rosenberger, T.A. (2009) Quantitative determination of free glycerol and myo-inositol from plasma and tissue by high-performance liquid chromatography, J. Chromatography B, Biomed Appl. 877: 3667-3672.

Willis, S., Ramakrishna, S., Rosenberger, T.A., Borges, K. (2009) Eicosapentaenoic and docosahexaenoic acids are not anticonvulsant or neuroprotective in acute mouse seizure models, Epilepsia 50: 138-142.

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) α-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 α-synuclein to brain arachidonate metabolism, Biochemistry 45: 6956-6966.

Bazinet, R.P., Weis, M.T., Rapoport, S.I., and Rosenberger, T.A. (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: 122-129.

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 altered by a six-day intra- cerebral ventricular infusion of bacterial lipopolysaccharide, J. Neurochem. 88: 1168-1178.

Bosetti, F., Weerasinghe, G., Rosenberger, T.A., and Rapoport, S.I. (2003) Valproic acid downregulates 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: 844-849.

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: 3887-2890.

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: 1205-121.

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. Chromatography 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.

Books Edited:

Methods in Signal Transduction Series, Lipid-mediated Signaling, Editors: Murphy, E.J. and Rosenberger, T.A. (2010) CRC Press, Florida

Book Chapters:

Dhaval P. Bhatt and Rosenberger, T.A. (2010) Methods for Kinetic Analysis of Fatty Acid Incorporation and Turnover in vivo: A Steady-State Kinetic Radiotracer Approach, in Methods in Signal Transduction: Lipid-mediated Signaling, CRC Press, Florida pp. 395-414.

Frieler, R.A., Watt, J.A., and Rosenberger, T.A. (2010) Methods of measuring the activity and expression of phospholipases C from mammalian tissue, in Methods in Signal Transduction: Lipid-Mediated Signaling, CRC Press, Florida pp. 27-54.

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.

Ph.D. (1994-1999), Medical Biochemistry, Ohio State University, Columbus, Ohio

Postdoctoral Fellow (1999-2004), National Institutes on Aging, National Institutes of Health, Bethesda, Maryland