The goal of this research is to understand the role of mitochondrial dysfunction and oxidative stress in Parkinson's disease (PD). These experiments will utilize both a novel in viovo model of PD as well a a cell culture model to elucidate the mechanisms by which complex I inhibition and oxidative damage result in neuronal cell death. Chronic, systemic rotenone treatment to rats will be used as a model of complex I dysfunction and selective nigrostriatal dopaminergic neurodegeneration seen in PD. Specifically, levels of aoxidative stress will be determined biochemically using an oxyblot technique. Regional distribution of oxidative damage will be studied using immunocytochemical protocols. Additionally, a c ell culture model in which cells are treated chronically with sublethal doses of rotenone will be used. In this system, we will use fluorescent techniques to determine whether chronic complex I dysfunction increases the susceptibility to cell death following exposure to apoptogenic agents. Finally, we will test new potential therapeutic agents for PD such as the antioxidant, coenzyme Q10 that also enhances mitochondrial function.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32NS011132-02
Application #
6539543
Study Section
Special Emphasis Panel (ZRG1-BDCN-2 (02))
Program Officer
Sheehy, Paul A
Project Start
2001-12-01
Project End
Budget Start
2001-12-01
Budget End
2002-11-30
Support Year
2
Fiscal Year
2002
Total Cost
$46,192
Indirect Cost
Name
Emory University
Department
Neurology
Type
Schools of Medicine
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322