Wayne State University

Aim Higher



College of Liberal Arts & Sciences
Department of Chemistry
Faculty Page
 
Tiffany A. Mathews
Title Assistant Professor
Division Analytical
Education B.S., State University of New York at Buffalo, 1998
Ph.D., Pennsylvania State University, 2003
Postdoctoral Fellow, Wake Forest University School of Medicine, 2004-2007
Office Chem 367
Phone (313)577-8660
E-Mail


Our research interests lie in the areas of neurodegenerative disease and neurochemical imbalances found in alcohol and drug abuse. Our studies concentrate on the biochemical and physiological pathways of these pathologies using in vivo bioanalytical methods to analyze neurotransmitter alterations in the brains of mice and rats. Normally neurons communicate through a complex set of chemical reactions that take place in milliseconds involving extremely low concentrations (picomolar) of neurotransmitters. Neurotransmitters such as biogenic amines, amino acids, peptides, and other small molecules are active in the pre and postsynaptic regions of neurons, but normal synaptic function can be disrupted by factors ranging from environmental conditions to genetic predisposition. Two monoamine neurotransmitters, serotonin and dopamine, receive a great deal of research attention because of the critical role they play in drug abuse involving alcohol and cocaine, psychiatric illnesses such as schizophrenia and depression, and in the degenerative diseases of Parkinsonism and Alzheimer's. We use state-of-the-art, in vivo, bioanalytical methods to investigate neurotransmitter reactions at the molecular level. Analytical chemistry has played a crucial role in understanding the dynamics of neurotransmitters by developing methods to measure minute concentrations of biological molecules in vivo as they flow from neuron to synapse and back.

Our laboratory uses voltammetry and microdialysis to assess the dynamics of the monoamine neurotransmitters dopamine and serotonin. Each technique measures different but complementary aspects of neurotransmitter function. Voltammetry records the release and uptake of dopamine and serotonin following electrical stimulation of brain slices with high temporal (100 msec) and spatial (10 um) resolution. Microdialysis, on the other hand, measures basal neurotransmitter levels and drug-induced changes with high sensitivity (1nM) and selectivity. Together, they provide a complete assessment of monoamine neurotransmitter dynamics and function.

Two of the lab's primary goals are to determine how brain derived neurotrophic factor or BDNF, a protein responsible for a neuron's growth and survival, influences monoamines during synaptic communication, and if any imbalance in the protein-neurotransmitter mix leads to the susceptibility of disease or drug abuse. A great deal of research has been performed on the dynamics of dopamine, but disease and addiction are probably not the result of a malfunction of one neurotransmitter any more than they are caused by a single gene or a problem with one protein. It is much more likely that disease and abuse are the result of the interaction of several biochemical processes. Recent studies have linked BDNF with an ability to modulate dopamine during neurotransmission which, in turn, may have an influence on the consumption of abused drugs and drug addiction. Our lab will begin to investigate any influences BDNF has on dopamine through the use of in vitro cyclic voltammetry and in vivo microdialysis. These studies will help us understand how BDNF affects the dopamine system as we go about mapping the complete series of chemical reactions in the BDNF-dopamine cycle. Our long term goal is to understand the basic physiology involved in the BDNF-dopamine cycle and apply that knowledge in seeking possible cures for certain neurodegenerative diseases and drug addiction.






Figure 1. Representative electrically evoked (1 pulse) dopamine (DA) signals in striatum slices from wildtype (C57/BL6) mice. From left to right: brain regions caudate-putamen, core and shell of the nucleus accumbens. Top Panel: data lines are voltammetry dopamine measurements taken every 100 ms. Bottom Panel: representative color plots. The voltammetric current (encoded on the z-axis) is plotted against the applied potential (y-axis) and the acquisition time (x-axis).



REPRESENTATIVE PUBLICATIONS

Mathews, T.A., Brookshire, B.R., Budygin, E.A., Goldwitz, D. and Jones, S.R., "A mouse model of hypdodopaminergia exhibits ethanol-induced hyperactivity," Submitted to Journal of Neurochemistry (2007).

Budygin, E.A., Olsen, E.O., Mathews, T.A., Diaz, M., Lack A.K., McCool B.A. and Jones S.R., "Effects of chronic alcohol exposure on dopamine uptake in rate nucleus accumbens and caudate putamen", accepted Psychopharmacology.

Mathews, T.A., John, C.E., Lapa, G.B., Budygin E.A. and Jones S.R., "No role of the dopamine transporter in acute ethanol effects on striatal dopamine dynamics," Synapse, 60(4): 288-94 (2006).

Jones, S.R., Mathews, T.A. and Budygin E.A., "Effect of moderate ethanol dose on dopamine uptake in rat nucleus accumbens in vivo," Synapse, 60(3): 251-255 (2006).

Goldowitz D., Matthews, D.B., Hamre, K.M., Mittleman, G, Chesler, E.J., Becker, H.C., Lopez, M.F., Jones, S.R., Mathews, T.A., Miles, M.F., Kerns, R., and Grant, K.A., "Progress in using mouse inbred strains, consomics and mutants to identify genes related to stress, anxiety and alcohol phenotypes," Alcohol Clinical and Experimental Research, 30(6): 1066-78 (2006).

Budygin E.A., Mathews, T.A., Lapa G.B. and Jones S.R., "Local effects of acute ethanol on dopamine neurotransmission in the ventral striatum of C57BL/6 mice," European Journal of Pharmacology, 523(1-3):40-5 (2005).

DEPARTMENT OF CHEMISTRY ©
5101 Cass Ave, Detroit, MI 48202
Phone: (313) 577-7784    Fax: (313) 577-8822