Andy’s Research

Now that I have graduated with my Ph.D. from Saint Louis University, I am a Postdoctoral Research Scholar at the University of Iowa in Iowa City, IA.

Throughout my graduate school experience, and now in my Postdoctoral research, I continue to work on basic principles underlying neurodegeneration, specifically with regards to causes of Parkinson’s Disease. Basically, a particular midbrain structure called the Substantia Nigra pars compacta sends signals in the form of the neurotransmitter dopamine to another structure in the forebrain called the Striatum. During the course of Parkinson’s disease, you lose those Substantia Nigra cells and, therefore, the dopamine they produce. Without dopamine in that specific location of the brain, you are unable to control your movements in a voluntary way. My research focuses on the reasons why those neurons of the Substantia Nigra are lost during the disorder.

In graduate school, while under the mentorship of Heather Macarthur, I worked on an oxidized form of dopamine called dopaminochrome (DAC). Again, the neurons lost during the course of Parkinson’s Disease produce dopamine, and in certain conditions, that dopamine can be converted to DAC which is harmful to the cells. My dissertation focused on the mechanisms by which DAC caused toxicity in MN9D cells, an immortalized cell line model for the Substantia Nigra neurons lost in Parkinson’s Disease. I found that the toxicity induced by DAC was directly related to oxidative stress, and that the cells died via caspase-independent apoptosis.

Currently, I work in the lab of Jonathan Doorn, at the College of Pharmacy at the University of Iowa. The lab is also researching the mode of cell death observed in Parkinson’s Disease, however we are focusing on a different molecule called 3,4-dihydroxyphenylaldehyde (DOPAL), a metabolite of dopamine that is also present in dopaminergic cells of the Substantia Nigra pars compacta. My portion of the project is looking at adducts of DOPAL on proteins, such that the presence of DOPAL may bind to and disrupt protein function, leading to cell death. Primarily, I am using HPLC and ESI-IT-MS/MS technologies to answer that question.

Publications:

  • Linsenbardt AJ, Wilken GH, Westfall TC, and Macarthur H. Cytotoxicity of dopaminochrome in the mesencephalic cell line, MN9D, is dependent upon oxidative stress, Neurotoxicology. (2009), 30: 1030 – 1035.

    • Abstracts:

  • Linsenbardt, A.J., Westfall, T.C. and Macarthur, H. (2007) Cytotoxicity of aminochromes in the mesencephalic cell line, MN9D, is dependent upon oxidative stress. Program No. 700.8. Society for Neuroscience, San Diego, CA
  • Linsenbardt, A.J., Wilken, G.H., Westfall, T.C. and Macarthur, H. (2008) Dopaminochrome, the oxidized product of dopamine, increases oxidative stress and decreases antioxidant defenses in MN9D cells. Program No. 140.11. Society for Neuroscience, Washington, D.C.
  • Linsenbardt, A.J., Wilken, G.H., Westfall, T.C. and Macarthur, H. (2009) The mechanism of cytotoxicity by dopaminochrome in MN9D cells. Program No. 828.16. Society for Neuroscience, Chicago, IL.
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