The long term goal of studies in my laboratory is to understand the role of lipid biomediators, in neuronal degeneration. Lipid biomediators include a wide range of compounds such as prostaglandins, leukotrienes, platelet activating factor lysophosphatidic acid (LPA), tumor necrosis factor and various cytokines. Currently, we are examining the role of LPA in signaling pathways associated with neuronal degeneration (apoptosis) as a model for Alzheimers disease and head trauma. We utilize primary neurons primary astrocytes, primary microglial cells and immortalized neuronally derived cultures cells (for gene transfer studies) as our model systems. These studies suggest that lipid biomediators, in particular LPA likely play a role in neuronal degeneration.
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Keller, J.N., Steiner, M.R., Mattson,M.P. and Steiner, S.M. Lysophosphatidic acid-induced signals in astrocytes. (1996) In Lipid Biomediators (ed. J.Y. Vanderhoek), Plenum Press, N.Y. pp. 223-228.
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Keller, J.N., Steiner, M.R., Mattson, M.P. and Steiner, S. M. (1996) Lysophosphatidic acid decreases glutamate and glucose uptake by astrocytes. J. Neurochem. 67, 2300-2305.
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Holtsberg, F.W., Steiner, M.R., Furukawa, K., Keller, J.N., Mattson, M.P. and Steiner, S.M.(1997) Lysophosphatidic acid induces a sustained elevation of neuronal intracellular calcium. J. Neurochem. 69, 68-75.
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Keller, J.N., Steiner, M.R., Holtsberg, F.W., Mattson, M.P. and Steiner, S.M. (1997) Lysophosphatidic acid-induced proliferation-related signals in astrocytes. J. Neurochem. 69, 1073-1084.
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Holtsberg, F.W., Steiner, M.R., Keller, J.N., Mark, R.J., Mattson, M.P. and Steiner, S.M., (1998) Lysophosphatidic acid induces necrosis and apoptosis in hippocampal neurons. J. Neurochem 70(1):66-76.
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Keller J.N., Kindy MS; Holtsberg, F.W., St Clair, D. K., Yen, H.C., Germeyer, A., Steiner S.M., Bruce-Keller, A. J., Hutchins J.B., Mattson M.P. (1998) Mitochondrial manganese superoxide dismutase prevents neural apoptosis and reduces ischemic brain injury suppression of peroxynitrite production, lipid peroxidation, and mitochondrial dysfunction. J Neurosci 18(2):687-97.
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Holtsberg, F.W., Steiner, M.R., Bruce-Keller, A.J., Keller, J.N., Mattson, M.P., Moyers, J.C., and Steiner, S.M. Lysophosphatidic acid and apoptosis of nerve growth factor-differentiated PC12 cells. J. Neurosci Res 53: 685-696.