Bioenergetic Defects and Oxidative Damage in Transgenic Mouse Models of Neurodegenerative Disorders.
Abstract
This study aims to determine what roles bioenergetic dysfunction and oxidative stress play in the etiology of neurodegeneration in Huntington's disease (HE) and familial amyotrophic lateral sclerosis (FALS), using transgenic mouse models. Studies in this first year employed C-14-2-deoxyglucose in vivo autoradiography and spectrophotometric metabolic enzyme assays. In the Hdh "knock-in" mouse model of HD we found no significant differences in cerebral glucose utilization between normal wild type mice (Hdh(Q7)) and mutant mice expressing 50 polyglutamines (Hdh(Q50)) at 4 months of age (a timepoint preceding pathologic changes). However, significant decreases in activities of the mitochondrial electron transport chain enzymes complexes I, II-III and IV were evident in cerebellum from Hdh(Q50) and Hdh(Q92) mice at this time point. In the G93A transgenic mouse model of FALS we found that cerebral glucose use is reduced in several forebrain regions at 60 days of age - a time point preceding the onset of the first pathological changes in these mice. In addition, complex I activity is increased in the forebrain of G93A mice at the same time point, consistent with the defect seen in FALS A4V patients with a SOD1 mutation. We have made significant progress towards the original goals of this proposal.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1999
- Accession Number
- ADA374141
Entities
People
- Susan Brown
Organizations
- Massachusetts General Hospital