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 (HE)) and amyotrophic lateral sclerosis (ALS), as previously reported. The current report period includes the first eleven months of work on the Consortium project "Mitochondrial Free Radical Generation in Parkinson's Disease", assessing in vivo whether mitochondria are the source of free radical generation in animal models of Parkinson's disease (PD). Studies in the first three years of this grant generated several exciting novel observations of presymptomatic energetic abnormalities in both HD and ALS models. In this period of the study, we have identified abnormalities in cerebral ATP generation in another mouse HD model (R6/2 mice), first evident around the age of symptom onset, and exacerbated as the phenotype progresses. We have also commenced studies examining the relationship between mitochondrial complex I inhibition and free radical-mediated oxidative damage. Using in vivo approaches we are optimizing dose and time-course studies after intracerebral administration of rotenone and pyridaben. We found increased lipid peroxidation and induction of the stress-response marker heme oxygenase-l shortly after rotenone administration, concomitant with complex I inhibition. These observations will be characterized further in the next year of study.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2003
- Accession Number
- ADA419306
Entities
People
- Susan E. Browne
Organizations
- Cornell University