- B.S., 1988, United States Air Force Academy
- M.S., 2000, University of Colorado , Denver
- Ph.D., 2002, University of Virginia
- Hereditary Disease Foundation Postdoctoral Fellow, University of North Carolina at Chapel Hill, 2002-2005
Areas of Specialization
Analytical Chemistry, Bioanalytical Chemistry, and Neurochemistry
Bioanalytical chemistry; microsensor development; microfluidics; electrochemical detection of neurotransmitters; fluorescence microscopy; neurological disorders; oxidative stress.
The goal of my research program is the development and application of bioanalytical techniques for studying how neurons communicate with each other. A wide array of techniques are employed, including fluorescence microscopy, caged compound photolysis, microfluidics, biochemical methods, behavioral techniques, and state-of-the-art electrochemical techniques that allow for the monitoring of biogenic molecules on physiologically relevant time scales. These methods are used to study a variety of important problems, including neurological disorders, oxidative stress, and mechanisms of drug action.
Huntington’s disease. Huntington’s disease (HD) is a neurodegenerative disorder characterized by uncontrollable muscle movements and mental illness. HD patients typically die 15 to 20 years following symptom onset. We and others have recently discovered that release of dopamine, a key neurotransmitter in motor and cognitive signaling, is sharply attenuated in animal models of HD. To understand the contributions of abnormal neurotransmitter release in the debilitating motor symptoms of HD, electrochemical techniques have been applied in vivo to animal models of HD. Additionally, microscopy techniques are applied to study tissue sections in these animal models to yield clues regarding mechanisms of altered signaling.
Chemobrain. “Chemobrain” is a decline in cognitive function experienced by patients undergoing chemotherapy treatment. Recent studies comparing cognitive function before and after chemotherapy suggest that approximately 20-30% of cancer patients will exhibit lower cognitive performance after chemotherapy than would be expected. Developing an understanding of chemobrain is becoming more important as the survival rates of cancers continue to increase. We are currently employing electrochemical and behavioral techniques in order to unravel the underlying mechanisms of chemobrain.
Oxidative Stress and Neurotransmission. A strong connection has been established between oxidative stress and many neurodegenerative disorders, including Parkinson’s disease, Alzheimer’s disease, and Lou Gehrig’s disease. We are interested in the effects of oxidative stress on neuronal function. Electrochemical and microscopy techniques are used to characterize release and uptake processes in models of oxidative stress.
Caged Compound Photolysis. Our research group is combining caged compound photolysis with fast-scan cyclic voltammetry measurements in order to resolve neurotransmitter interactions. Caged compounds are molecules that can release a molecular ‘cage’ upon exposure to light of sufficient energy. Here, we make use of the p-hydroxyphenacyl and coumarin cages to render bioactive molecules inactive. We then use a microscopy or a fiber-optic cable to supply ultraviolet and visible light in order to bioactivate the molecule on millisecond timescales. Immediate changes in neurotransmitter release are monitored using fast-scan cyclic voltammetry.
Microfluidic devices. We are pursuing the development and use of microfluidic devices for the study of neurotransmitter/neuromodulator release from brain slices. This approach will be combined with caged compound photoactivation as well.
Ortiz A. N., Osterhaus G. L., Lauderdale K., Mahoney L., Fowler S. C., von Hörsten S., Riess O., Johnson M. A. Motor function and dopamine release measurements in transgenic Huntington's disease model rats Brain Res. 2012, 1450:148-56. PMID: 22418060
Ortiz A. N., Kurth B. J., Osterhaus G. L., Johnson M. A. Impaired dopamine release and uptake in R6/1 Huntington's disease model mice. Neurosci. Lett. 2011, 492(1):11-14.
Ortiz A. N., Oien D. B., Moskovitz J., Johnson M. A. Quantification of reserve pool dopamine in methionine sulfoxide reductase A null mice. Neuroscience. 2011, 177:223-229. PMID: 21219974 PMC3449094
Fulks, J. L., O'Bryhim, B. E., Wenzel, S. K., Fowler, S. C., Vorontsova, E., Pinkston, J. W., Ortiz, A. N., Johnson, M. A. Dopamine Release and Uptake Impairments and Behavioral Alterations Observed in Mice that Model Fragile X Mental Retardation Syndrome. ACS Chem Neurosci. 2010, 1(10):679-690. PMC 2992329
Ortiz, A.N., Kurth, B.J., Osterhaus, G.L., Johnson, M. A. Dysregulation of intracellular dopamine stores revealed in the R6/2 mouse striatum. J Neurochem. 2010, 112(3):755-61. PMID:19929911
Oien DB, Ortiz AN, Rittel AG, Dobrowsky RT, Johnson MA, Levant B, Fowler SC, Moskovitz J. “Dopamine D(2) receptor function is compromised in the brain of the methionine sulfoxide reductase A knockout mouse,” J Neurochem. 2010, 114(1):51-61. PMID: 20374422 PMC2933736
Miller, B.R., Walker, A. G., Fowler, S. C., von Horsten, S., Riess, O., Johnson, M. A., Rebec, G. V. “Dysregulation of coordinated firing patterns in striatum of freely behaving transgenic rats that model Huntington’s disease,” Neurbiology of Disease, 2010, 37, 106-113.
Fowler S. C., Miller B. R., Gaither T. W., Johnson M. A., Rebec G. V., “Force-plate quantification of progressive behavioral deficits in the R6/2 mouse model of Huntington’s disease,” Behav. Brain Res. 2009, 24;202(1):130-7. PMID: 19447289
Kraft, J. C., Osterhaus, G. L., Ortiz, A. N., Garris, P. A., Johnson, M. A., “In Vivo Dopamine Release and Uptake Impairments in Rats Treated with 3-Nitropropionic Acid,” Neuroscience, 2009, 161(3):940-9. PMID: 19362126
Osterhaus, G. L., Selley, P., Silcio, K., Lauderdale, K., Fowler, S. C., von Horsten, S., Riess, O., Johnson, M. A. (2008) “Simultaneous microdialysis and force-plate actometer measurements obtained in transgenic Huntington’s disease model rats,” in Monitoring Molecules in Neuroscience, eds. PEM Phillips, SG Sandberg, S Ahn, and AG Phillips. University of British Columbia Press, Vancouver, BC
Oien, D. B., Osterhaus, G. L., Latif, S. A., Pinkston, J. W., Fulks, J., Johnson, M., Fowler, S. C., Moskovitz, J. “MsrA knockout mouse exhibits abnormal behavior and brain dopamine levels,” Free Rad. Biol. Med. 2008, 45(2):193-200. PMID: 18466776