- B.A. in Biology, Cornell University, Ithaca, NY
- Ph.D. in Neuroscience, University of Maryland, Baltimore
- Postdoctoral Fellowship, Cell Death, John Hopkins University, Baltimore, MD
- Staff Scientist, Mechanisms of Neurodegeneration, The Buck Institute for Age Research, Novato, CA
Limiting damage to mitochondria, the primary energy-generating organelles of the cell, is crucial for neuroprotection. My laboratory studies basic subcellular mechanisms that govern cell death and survival in neurodegenerative disorders, with a focus on mitochondrial bioenergetics. Past investigations have centered on two key pathways of injury, caspase-dependent apoptotic cell death regulated by Bcl-2 family proteins and caspase-independent cell death mediated by calcium overload and mitochondrial dysfunction. Our current NIH-funded project focuses on how inflammatory microglial activation exacerbates neuronal injury through nitric oxide production and how oxygen availability influences the mechanisms of injury. Additionally, we are investigating the function of mitochondrial remodeling mediated by the fission GTPase Drp1 in activated microglial cells. We have pioneered the development and implementation of two novel applications of Seahorse Bioscience Extracellular Flux Technology, real-time assessment of mitochondrial respiration within permeabilized primary neurons and from whole brain tissue slices, expanding the ways in which mitochondrial function can be studied in cells of the central nervous system.
Lab Techniques and Equipment:
- Primary cortical neuron and microglia cell culture
- Real-time measurement of cellular oxygen consumption and glycolysis rates (Seahorse Bioscience XF24 Extracellular Flux Analyzer)
- Live-cell fluorescent imaging of:
- mitochondrial membrane potential (e.g. using TMRM)
- reactive oxygen species (e.g. using dihydroethidium)
- intracellular calcium changes (e.g. using fluo indicators)
- mitochondrial remodeling (e.g. using mito-YFP)
- Fluorescence-based cell death assays (e.g. propidium iodide, Annexin V, Yo-Pro-1)
- Isolated mitochondria assays, including measurements of membrane potential, calcium uptake, oxygen consumption, and reactive oxygen species generation
- Enzyme assays, western blot, ELISA, standard biochemistry techniques, immunocytochemistry
- Electron microscopy
Novel Mechanisms of Microglial Neurotoxicity at Physiological Oxygen
NIH/NINDS R01 NS085165
Mitochondrial and Neuronal Protection by GGF2
Acorda Therapeutics Study Number GG-Mito-Pol-1
Chinta, S.J., Rane, A., Yadava, N., Andersen, J.K., Nicholls, D.G., and Polster, B.M. (2009) Reactive oxygen species regulation by AIF- and complex I-depleted brain mitochondria. Free Radic Biol Med 46: 939-47.
Gerencser, A.A., Mark, K.A., Hubbard, A.E., Divakaruni, A.S., Mehrabian, Z., Nicholls, D.G., and Polster, B.M. (2009) Real-time visualization of cytoplasmic calpain activation and calcium deregulation in acute glutamate excitotoxicity. J Neurochem 110: 990-1004.
Khairallah, R.J. Sparagna, G.C., Khanna, N., O’Shea, K.M., Hecker, P.A., Kristian, T., Fiskum, G., Des Rosiers, C., Polster, B.M., and Stanley, W.C. (2010) Dietary Supplementation with Docosahexaenoic Acid, but Not Eicosapentanoic Acid, Dramatically Alters Cardiac Mitochondrial Phospholipid Fatty Acid Composition and Prevents Permeability Transition. Biochimica et Biophysica Acta 1797: 1555-1562.
Schuh, R.A., Clerc, P., Hwang, H., Mehrabian, Z., Bittman, K., Chen, H., and Polster, B.M. (2011) Adaptation of microplate-based respirometry for hippocampal slices and analysis of respiratory capacity. J Neurosci Res 89: 1979-1988.
Zhang, Z., Wakabayashi, N., Wakabayashi, J., Tamura, Y., Song, W., Sereda, S., Clerc, P., Polster, B.M., Aja, S.M., Pletnikov, M.V., Kensler, T.W., Shirihai, O.S., Iijima, M., Hussain, M.A., and Sesaki, H. (2011) The dynamin-related GTPase Opa1 is required for glucose-stimulated ATP production in pancreatic beta cells. Mol Biol Cell 22: 2235-2245.
Wang, H., Sreenevasan, U., Hu, H., Saladino, A., Polster, B.M., Lund L.M., Gong D.W., Stanley W.C., and Sztalryd, C. (2011) Perilipin 5, lipid droplet associated protein provides physical and metabolic linkage to mitochondria. J Lipid Res 52: 2159-2168.
McCranor, B.J., Bozym, R.A., Vitolo, M.I., Fierke, C.A., Bambrick, L., Polster, B.M., Fiskum, G., and Thompson, R.B. (2012) Quantitative Imaging of Mitochondrial and Cytosolic Free Zinc Levels in an in vitro Model of Ischemia/Reperfusion. J Bioenerg Biomembr 44: 253-63.
Khairallah, R.J., Kim, J., O’Shea, K.M., O’Connell,K.A., Brown, B.H., Galvao, T., Daneault, C., Christine Des Rosiers, C., Polster, B.M., Hoppel, C.L., and Stanley, W.C. (2012) Improved Mitochondrial Function with Diet-Induced Increase in Either Docosahexaenoic Acid or Arachidonic Acid in Membrane Phospholipids. PLoS ONE 7: e34402.
Clerc, P. and Polster, B.M. (2012) Investigation of Mitochondrial Dysfunction by Sequential Microplate-based Respiration Measurements from Intact and Permeabilized Neurons. PLoS ONE 7: e34465.
Clerc, P., Carey, G.B., Mehrabian, Z., Wei, M., Hwang, H., Girnun, G.D., Chen, H., Martin, SS., and Polster, B.M. (2012) Rapid Detection of an ABT-737-sensitive Primed for Death State in Cells Using Microplate-based Respirometry. PLoS ONE 7: e42487.
Polster, B.M. (2013) AIF, reactive oxygen species, and neurodegeneration: a “complex” problem. Neurochem Int 62: 695-702.
Laird, M.D., Clerc, P., Polster, B.M., and Fiskum, G. (2013) Augmentation of Normal and Glutamate-Impaired Neuronal Respiratory Capacity by Exogenous Alternative Biofuels. Transl Stroke Res 4: 643-651.
Clerc, P, Young, C.A., Bordt, E.A., Grigore, A.M., Fiskum, G., and Polster, B.M. (2013) Magnesium Sulfate Protects Against the Bioenergetic Consequences of Chronic Glutamate Receptor Stimulation. PLoS ONE 8: e79982.
Clerc, P. Ge, S.X., Hwang, H., Waddell, J., Roelofs, B.A., Karbowski, M., Sesaki, H., and Polster, B.M. (2014) Drp1 is dispensable for apoptotic cytochrome c release in primed MCF10A and fibroblast cells but affects Bcl-2 antagonist-induced respiratory changes. Br J Pharmacol 171:1988-1999
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