Fundamental Patterns Underlying Neurotoxicity Revealed by DNA Microarray Expression Profiling
Abstract
The selective neurotoxins l-methyl-l,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine (6-OHDA) have been widely used to generate animal models of Parkinson's Disease (PD). To understand and order the genetic events associated with these neurotoxins, DNA microarray technology has been used to monitor differences in gene expression patterns in normal versus pathological conditions. Eleven thousand murine genes and expressed secuence tags were screened to determine changes in gene expression caused by MPP+, the active metabolite of MPTP, and 6-OHDA in a mouse CNS dopaminergic cell line. These studies were facilitated by an in-house Genechip Facility providing microarrays, services and software. Data derived from either toxin paradigm was compared to identify transcriptional changes associated with parkinsonism-inducing neurotoxins. Present findings indicate that both of these neurotoxins induce ER stress although not to the same degree. Identification of key genetic components of this response may suggest new points of intervention. Taken together, these experiments will help clarify the molecular mechanisms associated with 6-OHDA and MPP+ toxici ty and might aid in developing novel therapeutic avenues to pursue relevant to PD.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2002
- Accession Number
- ADA409422
Entities
People
- Karen L. O'malley
Organizations
- University of Washington