Ronald B. Tjalkens, Ph.D.
Phone: (970) 491-7168
Fax: (970) 491-7569
Office: 131 Physiology Building
- Ph.D., Toxicology, University of Colorado Health Sciences Center
- B.S., Chemistry/Biochemistry, University of California at San Diego
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.
• 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
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,
, 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.
Environmental & Radiological Health Sciences
1681 Campus Delivery
Colorado State University
Fort Collins, CO 80523
Phone: (970) 491-7038
Fax: (970) 491-2940