The primary focus of my research is on determining the role of environmental toxins in neurodegenerative diseases. The main neurodegenerative diseases, Alzheimer’s, Parkinson’s, and amytrophic lateral sclerosis (ALS) are all similar in that the disease is usually caused by a combination of genetic predisposition and environmental factors. However, what those environmental factors are is completely unknown. We use cell culture methods to study the mechanism of toxicity of a number of potential candidates, including mercury, pesticides, and BMAA. BMAA is a non-protein amino acid that was first implicated in neurodegenerative diseases on the pacific island of Guam, but recent evidence suggests that it may be involved in triggering the onset of neurodegenerative diseases throughout the world. The goal of the research is to determine how environmental toxins interact with genetic predisposition to cause neurodegenerative diseases and to determine how to prevent those conditions.
A second area of interest is the toxicity of dental materials. The use of dental amalgam is controversial because it contains mercury. However, many dental materials have the potential to release toxic compounds. The particular focus is on the use of growth factors to alter the differentiation of dental pulp cells in an attempt to make them resistant to the toxicity of dental materials. Currently, if when treating a cavity, the dental pulp is exposed, there is a very high probability that it will die and a root canal will be required. Growth factors are naturally occurring substances that alter differentiation and survival of cells. We are testing whether specific growth factors alter the differentiation of dental pulp cells in ways that allow them to survive contact with dental materials.
- Bridges R, Lutgen V, Lobner D, Baker DA. Thinking outside the cleft to understand synaptic activity: contribution of the cystine-glutamate antiporter (System xc-) to normal and pathological glutamatergic signaling. Pharmacol Rev. 2012;64:780-802.
- Rush T, Liu XQ, Nowakowski AB, Petering DH, Lobner D. Glutathione-mediated
neuroprotection against methylmercury neurotoxicity in cortical culture is dependent on M
RP1. Neurotox. 2012;33:476-481.
- Rush T, Liu XQ, Lobner D. Synergistic toxicity of the environmental neurotoxins
methylmercury and b-N-methylamino-L-alanine. Neuroreport. 2012;23:216-219.
- Liu X, Resch J, Rush T, Lobner D. Functional upregulation of system xc- by fibroblast growth factor-2. Neuropharm. 2012;62:901-906.
- Pauly K, Fritx K, Furey A, Lobner D. Insulin-like growth factor 1 and transforming
growth factor-b stimulate cystine/glutamate exchange activity in dental pulp cells. J Endo. 2011;37:943-947.
- Furey A, Hjelmhaug J, Lobner D. Flow Line, Durafill VS, and Dycal toxicity to dental pulp cells: effects of growth factors. J Endo. 2010;36:1149-1153.
- Slotkin TA, Lobner D, Seidler FJ. Transcriptional profiles of glutamate transporters
reveal differences between organophosphates but similarities with unrelated neurotoxicants. Brain Res Bull. 2010;83:76-83.
- Rush T, Liu X, Hjelmhaug J, Lobner D. Mechanisms of chlorpyrifos and diazinon induced neurotoxicity in cortical culture. Neurosci. 2010;166:899-906.
- Madayag A, Kau K, Lobner D, Mantsch J, Baker D. Drug-Induced Plasticity Contributing to Heightened Relapse Susceptibility: Neurochemical Changes & Augmented Reinstatement in High-Intake Rats. J Neurosci. 2010;30:210-217.
- Liu X, Rush T, Ciske J, Lobner D. Selective death of cholinergic neurons induced
by β-methylamino-L-alanine. Neuroreport. 2010;21:55-58.
- Lobner D. Mechanisms of beta-N-methylamino-L-alanine induced neurotoxicity. Amyotrophic Lateral Sclerosis. 2009;Suppl 2:56-60.
- Connaughton K, Foronda J, Lobner D. Response to protocol review scenario: Not a
shortcut. Lab Anim. 2009;38:226-227.
- Rush T, Hjelmhaug J, Lobner D. Effects of chelators on mercury, iron, and lead
neurotoxicity in cortical culture. Neurotox. 2009; 30:47-51.
- Liu X, Rush T, Zapata J, Lobner D. beta-N-methylamino-L-alanine induces oxidative stress and glutamate release through action on system Xc(-). Exp Neurol. 2009;217:429-433.