people
|Faculty
|Adrian Michael
 |
Adrian Michael Department of Chemistry |
Monitoring chemical processes in living animals is a challenging analytical task. This is especially true in the central nervous system, where information is carried between neurons by very low levels of very short-lived substances, called neurotransmitters. Monitoring neurotransmitters in living animals has been so difficult that most neurochemical studies are performed on dissected brain tissue, which makes it difficult to know what the results tell us about the living brain. The development of new analytical tools will enable a better understanding of the central nervous system and, in turn, facilitate improvements in human neurological health. This lab is focussed on the development of minute analytical devices, either sensors or sampling devices, that can be used to monitor selected neurochemicals in brain extracellular fluid. Much of our work uses electroanalytical techniques in conjunction with microelectrodes, which have dimensions of just a few micrometers. These tiny electrodes are well suited to brain research because they cause very little damage to the delicate tissue. Some of our electrodes are even smaller than the cells of the brain. Please visit our group homepage to view some pictures of our electrodes taken with an electron microscope.
With these microelectrodes we are able to monitor the neurotransmitters called catecholamines. Catecholamines are important in movement control, stress, drug abuse, and Parkinson's disease. By immobilizing enzymes onto the electrode, we can develop microsensors for the enzyme substrate. Recently, we have demonstrated that this strategy can be used to monitor choline in brain tissue and we are now working towards a microsensor for acetylcholine, the transmitter that seems to go wrong in Alzheimer's disease.
While the microelectrodes have many advantages, many compounds important in brain function, such as peptides and proteins, are not amenable to electrochemical techniques. So, we are also devising techniques for collecting and analyzing nanoliter-sized samples of extracellular fluid. The goal here is to construct devices just as small as the microelectrodes in order to keep tissue damage at the smallest possible level. In vivo experiments with these devices are just now getting underway.
Selected Publications
"Voltammetric study of extracellular dopamine near nicrodialysis probes acutely implanted in the striatum of the anesthetized rat," L. M. Borland, G. Shi, H. Yang, A. C. Michael, J. Neurosci. Methods, 2005, in press
"A theory for the impact of basal turnover on dopamine clearance kinetics in the rat striatum after MFB simulation and pressure-ejection," A. C. Michael, L. M. Borland, J. J. Mitala, B. M. Willoughby, C. M. Motzko, J. Neurochem., 2005, in press
"Ultrastructure at carbon fiber microelectrode implanatation sites after acute voltammetric measurements in the striatum of anesthetized rats," J. L. Peters, L. H. Miner, A. C. Michael, S. R. Sesack, J. Neurosci. Methods, 2004, 137, 9-23
"Voltammetric study of the control of striatal dopamine release by glutamate," L. M. Borland, A. C. Michael, J. Neurochem., 2004, 91, 220-229
"Monitoring hydrogen peroxide in the extracellular space of the brain with amperometric microsensors," N. V. Kulagina, A. C. Michael, Anal. Chem., 2003, 75, 4875-4881
"Invasive consequences of using microelectrodes and microdialysis probes in the brain," A. S. Khan, A. C. Michael, Trends in Analytical Chemistry, 2003, 22, 503-508
"Carbon fiber microelectrodes for in the vivo measurement of neurotransmitters: A close-up look at neurochemical activity in the brain.," J. L. Peters, N. V. Kulagina, H. Yang, A. C. Michael, In Encyclopedia of Electrochemistry, Vol. 9, Bioelectrochemistry, Bard AJ, Stratmann M, and Wilson GS, eds. Wiley, Weinheim, Germany., 2002,
"Carbon fiber microelectrodes with multiple sensing elements for in vivo voltammetry," S. F. Dressman, J. L. Peters, A. C. Michael, J. Neurosci. Methods, 2002, 119, 75-81
"Glutamate regulates the spontaneous and evoked release of dopamine in the rat striatum," N. V. Kulagina, M. J. Zigmond and A. C. Michael, Neuroscience, 2001, 102, 121-128
"Pharmacological evidence for the selectivity of in vivo signals obtained with enzyme-based electrochemical sensors," J. Cui, N. V. Kulagina and A. C. Michael, J. Neurosci. Methods, 2001, 104, 183-189