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Dr. Tjalkens in his lab-a dark haired man wearing a lab coat sitting at a table behind a microscope

Ronald B. Tjalkens, Ph.D.
Associate Professor

Phone: (970) 491-7168
Fax: (970) 491-7569
Email: Tjalkens@rams.colostate.edu
Office: 131 Physiology Building

 

Degrees

Research Interests

Dr. Tjalkens is a faculty member of the Graduate program in Molecular, Cellular and Integrative Neuroscience, part of the interdisciplinary program in Cell and Molecular Biology. His research interests are in astrocyte biology and calcium signaling, mitochondrial dysfunction in neurodegenrative disorders, and molecular regulation of neuro-inflammatory genes.

"A central focus of research in our laboratory is the role of astrocytes in modulating neuronal function, both in normal physiology and in neurodegenerative disorders. Astrocytes are the principal non-neuronal cell type of the central nervous system and maintain neuronal homeostasis through provision of metabolic intermediates for ATP synthesis, modulation of neurotransmitter uptake, and protection against oxidative stress through the release of antioxidants. It has been recently discovered that astrocytes communicate through large intercellular networks via slow calcium waves that are propagated by the release of ATP following stimulation by neuronal synaptic activity. These calcium waves are now known to be critical to modulating synaptic activity and protecting against excessive excitatory neurotransmission. We use a variety of real-time fluorescence imaging techniques to probe the role that mitochondrial dysfunction (such as that observed in Parkinson’s disease) plays in altering normal calcium signaling in astrocytes and in contributing to aberrant neuro-glial interactions. In pursuit of these questions, a number of neurotoxicants are employed to disrupt normal mitochondrial function in cells and transgenic animals, including the dietary metal, manganese (Mn 2+) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a synthetic heroin derivative that has produced irreversible parkinsonism in humans."

Molecular regulation of neuro-inflammatory genes

Another area of research interest involves the role of inflammatory activation of glial cells in neurodegeneration. Increased production of inflammatory cytokines and nitric oxide (NO) by activated astrocytes cells damages adjacent neurons and contributes to the progression of injury in neurodegenerative disorders such as Parkinson’s disease. Production of NO in glial cells is regulated by protein signaling cascades and by nuclear receptors, such as the peroxisome proliferator-activated receptor gamma (PPARγ) and retinoid X receptor (RXR), that modulate transcriptional activation of inflammatory genes including inducible nitric oxide synthase (NOS2). Inducible expression of NOS2 is principally regulated by the transcription factor, nuclear factor kappa B (NF- κß), that is activated by multiple upstream signaling events, such as phosphorylation cascades, plasma membrane receptors, and oxygen radicals. It has recently been demonstrated that pharmacologic agonists of PPARγ are powerfully neuroprotective in models of Parkinson’s disease, but a molecular understanding of the mechanism by which these compounds exert their neuroprotective effects is lacking. PPARγ gamma has been shown to interact with the p65 subunit of NF- κß in certain cell types but similar interactions in neural cells have not been described. Lack of this knowledge is an important problem, because it prevents understanding the mechanism by which nuclear receptors regulate the production of NO within glia and thus, the development of new therapeutic modalities designed to exploit these regulatory properties.

Selected Publications

 •  Aschner M, Erikson KM, Herrero Hernández E, and Tjalkens R. Manganese and its Role in Parkinson's Disease: From Transport to Neuropathology. Neuromolecular Med. 2009 Sep 4. [Epub ahead of print]

 • Moreno JA, Yeomans EC, Streifel KM, Sullivan KA, Brattin B, Taylor R, and Tjalkens RB. Age-dependent susceptibility to manganese-induced neurological dysfunction. Toxicol Sci. 2009 Dec;112(2):394-404

 • Moreno JA, Streifel KM, Sullivan KA, Legare ME, and Tjalkens RB. Developmental exposure to manganese (Mn) increases adult susceptibility to inflammatory activation of glia and neuronal protein nitration. Toxicol Sci. 2009 Dec;112(2):405-15

 • Carbone DA, Popichak KA, Moreno JA, Safe S, and Tjalkens RB. Suppression of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced nitric oxide synthase 2 expression in astrocytes by a novel diindolyl methane analog protects striatal neurons against apoptosis. Mol. Pharmacol. 75(1):35-43, 2009

 • Ashley AK, Hanneman WH, Moreno JA, Pollack A, Tjalkens RB, Legare ME. Analysis of targeted mutation in DJ-1 on cellular function in primary astrocytes.Toxicol Lett. 184(3):186-91, 2009

 • Carbone DA, Moreno JA, and Tjalkens RB. Nuclear Factor Kappa-B Mediates Selective Induction of Neuronal Nitric Oxide Synthase in Astrocytes During Low-Level Inflammatory Stimulation with MPTP. Brain Res, 217:1-9, 2008

 • Moreno JA, Sullivan KA, Carbone DA, Hanneman WH, and Tjalkens RB. Manganese potentiates NF-κB-dependent expression of nitric oxide synthase 2 in astrocytes by activating soluble guanylate cyclase and extracellular regulated kinase signaling pathways J. Neurosci. Res. 86:618–629, 2008

 • Dooley GP, Reardon KF, Prenni JE, Tjalkens RB, Legare ME, Foradori CD, Tessari JE, Hanneman WH. Proteomic analysis of diaminochlorotriazine adducts in wister rat pituitary glands and LbetaT2 rat pituitary cells. Chem Res Toxicol. 21(4):844-51, 2008

 • Tjalkens RB, Liu X, Mohl B, Wright T, Carbone DL, Moreno JA, and Safe S. The peroxisome proliferator-activated receptor-gamma agonist 1,1-bis(3'-indolyl)-1-(p-trifluoromethylphenyl) methane suppresses manganese-induced production of nitric oxide in astrocytes and inhibits apoptosis in co-cultured PC12 cells. J. Neurosci. Res. 15;86(3):618-29. Feb 2008

 • Tjalkens RB, Zoran M, Mohl B, and Mouneimne R. Manganese suppresses ATP-dependent intercellular calcium waves in astrocyte networks through alteration of mitochondrial and endoplasmic reticulum calcium dynamics, Brain Res. 1113, 210-219, 2006.

 • Liu X., Sullivan K.A., Madl J.E., Legare M., and Tjalkens R.B. Manganese-induced neurotoxicity: the role of astroglial-derived nitric oxide in striatal interneuron degeneration, Toxicol. Sci. 91(2):521-531, 2006.

 • Peters JL, Earnest BJ, Tjalkens RB, Cassone VM, Zoran MJ. Modulation of intercellular calcium signaling by melatonin in avian and mammalian astrocytes is brain region-specific. J. Comp. Neurol. 493(3):370-380, 2005.

 • Liu X, Buffington JA, and Tjalkens RB. Astroglial-mediated neuronal apoptosis following exposure to manganese and cytokines requires NF-kB-dependent production of nitric oxide Mol Brain Res 141(1): 39-47, 2005.

 • Ng Y, Barhoumi R, Tjalkens RB, Fan YY, Kolar S, Wang N, Lupton JR, and Chapkin RS. The role of docosahexaenoic acid in mediating mitochondrial membrane lipid oxidation and apoptosis in colonocytes. Carcinogenesis(June 23; E-pub ahead of print) 2005

 • Mounemne R., Faske J., Liu X., and Tjalkens R.B., Manganese potentiates lipopolysaccharide-induced expression of NOS2 in C6 glioma cells through mitochondrial-dependent activation of nuclear factor kappa B. Mol. Brain Res. (122): 167-179, 2004

 • Tjalkens, R.B., Phelka, A.D., Beck, M.J., and Philbert, M.A. Regional variation in the activation threshold for 1,3-dinitrobenzene-induced mitochondrial permeability transition (MPT) in brainstem and cortical astrocytes. Neurotoxicol 24(3):391-401, 2003

 • McQueen , C.A. , Chau, B., Erickson, R.P., Tjalkens, R.B., and Philbert, M.A. The effects of genetic variation in N-acetyltransferases on 4-aminobiphenyl genotoxicity in mouse liver. Chemico-Biological Interact. 146(1):51-60 ., 2003

 • Miller T.J., Phelka A.D., Tjalkens R.B., Dethloff L.A., and Philbert M.A., CI-1010 Induced Opening of the Mitochondrial Permeability Transition Pore Precedes Oxidative Stress and Apoptosis in SY5Y Neuroblastoma Cells, Brain Research 963:43-56, 2003.

 • McQueen , C.A. , Mitchell, K.M., Dang, L.N., Chau, B., Tjalkens, R.B., and Philbert, M.A. Prenatal expression of N- acetyltransferases in C57Bl/6 mice. Chemico. Biol. Interact 145: 77-87, 2003.

 • Brasuel, M., Kopelman, R., Miller, T.J., Tjalkens, R., and Philbert, M.A. Fluorescent Nanosensors for Intracellular Chemical Analysis: Decyl Methacrylate Liquid Polymer Matrix and Ion Exchange Based Potassium PEBBLE Sensors With Real Time Application to Viable Rat C6 Glioma Cells. Anal. Chem. 73(10): 2221-2228, 2001.

 • Taneja, N., Tjalkens, R., Philbert, M.A., and Rehemtulla, A. Mitochondria as the Primary Target for Ionizing Radiation-Induced Apoptosis.Oncogene, 20: 167-177, 2001.

 • Tjalkens, R.B. , Ewing, M., and Philbert, M.A. Differential cellular regulation of the mitochondrial permeability transition in an in vitro model of 1,3-dinitrobenzene-induced encephalopathy. Brain. Res., 874(2): 165-177, 2000.

Mailing Address
Environmental & Radiological Health Sciences
1681 Campus Delivery
Colorado State University
Fort Collins, CO 80523
Phone: (970) 491-7038
Fax: (970) 491-2940
Email: ERHSDepartment