An increased production of reactive oxygen species is thought to be critical to the pathogenesis of Parkinson's disease. Furthermore, a growing body of evidence indicates that alterations in the glutathione system, and specifically the detoxification of hydrogen peroxide by glutathione peroxidase (GPx), may play a central role in the development of this oxidative stress. In this study, we will use GPx knockout (GPxKO) mice and recombinant adenoviruses to examine the significance of GPx and glutathione (GSH) to the survival of dopaminergic neurons. In addition, we will investigate how adding the putative exogenous source of free radical 1-methyl-4-phenylpyridine affects the role of GPx in handling oxidative stress in dopaminergic neurons. We will begin by examining the survival of dopaminergic neurons in dissociated mesencephalic cultures which are designed to minimize glial contamination. In addition, we will use digital imaging microfluorimetry to measure levels of free radicals and GSH in individual dopaminergic and nondopaminergic neurons. Subsequently, we will use an in vivo paradigm to study the GSH system in a more physiologic environment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30MH011986-02
Application #
6134825
Study Section
Molecular, Cellular, and Developmental Neurobiology Review Committee (MCDN)
Program Officer
Goldschmidts, Walter L
Project Start
1998-07-01
Project End
Budget Start
1999-09-15
Budget End
2000-06-30
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Chicago
Department
Neurology
Type
Schools of Medicine
DUNS #
225410919
City
Chicago
State
IL
Country
United States
Zip Code
60637