Ronald B. Tjalkens, Ph.D.
Associate Professor

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

Degrees

• Ph.D., Toxicology, University of Colorado Health Sciences Center
• B.S., Chemistry/Biochemistry, University of California at San Diego

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."

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