Bioenergetic Defects and Oxidative Damage in Transgenic Mouse Models of Neurodegenerative Disorders
Abstract
The initial three years of this project determined the contributions of bioenergetic defects and oxidative stress to neurodegeneration in Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS), as previously reported. The current report period covers the second year of work on the Consortium project "Mitochondrial Free Radical Generation in Parkinson's Disease", which was appended to the original grant number. This project is to assess in vivo whether mitochondria are the source of free radical generation in animal models of Parkinson's disease (PD). In this period of the study we have continued studies examining the relationship between mitochondrial complex I inhibition and free radical-mediated oxidative damage. Using in vivo approaches we are optimizing the doses and time-courses for detection of complex I inhibition and reactive oxygen species (ROS) generation after intracerebral administration of rotenone and pyridaben. We have found increased production of the DNA oxidative damage marker 8-hydroxydeoxyguanosine (8-OHdG) shortly (1 hour) after rotenone injection into rat striatum. Lipid peroxidation and induction of the stress-response marker heme oxygenase- 1 follow DNA oxidation, concomitant with complex I inhibition. Due to an unforeseen change in personnel, a no-cost extension of one year was requested, and granted, to complete these studies in the forthcoming year.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2004
- Accession Number
- ADA430585
Entities
People
- Susan E. Browne
Organizations
- Cornell University