Throughout my graduate school experience, and in my previous Postdoctoral research, I worked on basic principles underlying neurodegeneration, specifically with regards to causes of Parkinson’s Disease. Essentially, 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 focused 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.
After graduate school, I worked in the lab of Jonathan Doorn, at the College of Pharmacy at the University of Iowa. This lab is also researching the mode of cell death observed in Parkinson’s Disease, however we focused 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 looked 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 used HPLC and ESI-IT-MS/MS technologies to answer that question.
Now, I work in the lab of Steven Mennerick in the Department of Psychiatry at Washington University. My research here represents something of a departure from previous work in neurodegeneration, as I now am studying synaptic transmission, specifically the elecrophysiological properties of the NMDA receptor. This work does not necessarily relate to any one disorder, however NMDA receptor function is extremely important in research areas impacting epilepsy, long-term potentiation/depression (i.e. the mechanism underlying memory), and schizophrenia.
- 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.
- Linsenbardt AJ, Breckenridge JM, Wilken GH, and Macarthur H. Dopaminochrome induces caspase-independent apoptosis in the mesencephalic cell line, MN9D. J Neurochem. (2012), 122: 175 – 184.
- Linsenbardt AJ, Chisari M, Yu, A, Shu, HJ, Zorumski CF, and Mennerick S. Noncompetitive, voltage-dependent NMDA receptor antagonism by hydrophobic anions. Molecular Pharmacology. (2013), 83: 354 – 366.
- Paul, SM, Doherty, J.J., Robichaud, AJ, Belfort, GM, Chow, BY, Hammond, RS, Crawford, DC, Linsenbardt, AJ, Shu, HJ, Izumi, Y, Mennerick, SJ, and Zorumski, C.F. The major brain cholesterol metabolite 24(S)-hydroxycholesterol is a potent allosteric modulator of N-methyl-D-aspartate receptors. J. Neurosi. (2013), 33: 17290 – 17300.
- 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.
- Linsenbardt, A.J., Doorn, J.A. (2010) Covalent modification of the dopamine metabolite 3,4-dihydroxyphenylacetaldehyde to peptides. Central States Society of Toxicology Annual Meeting, Iowa City, IA.
- Linsenbardt, A.J., Doorn, J.A. (2011) The dopamine metabolite, 3,4-dihydroxyphenylacetaldehyde, covalently modifies peptides and proteins. MIKI 2011, Lawrence, KS.
- Linsenbardt AJ, Chisari M, Zorumski CF, and Mennerick S. (2012) Non-competitive, voltage-dependent NMDA receptor antagonism by hydrophobic anions. Society for Neuroscience, New Orleans, LA.