Email this page

Print this page

Research Paper

Comparative prion disease gene expression profiling using the prion disease mimetic, cuprizone

Laura R. Moody, Allen J. Herbst, Han Sang Yoo, Joshua P. Vanderloo and Judd M. Aiken

This is an open-access article

 Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.

Identification of genes expressed in response to prion infection may elucidate biomarkers for disease, identify factors involved in agent replication, mechanisms of neuropathology and therapeutic targets.  Although several groups have sought to identify gene expression changes specific to prion disease, expression profiles rife with cell population changes have consistently been identified.  Cuprizone, a neurotoxicant, qualitatively mimics the cell population changes observed in prion disease, resulting in both spongiform change and astrocytosis.  The use of cuprizone-treated animals as an experimental control during comparative expression profiling allows for the identification of transcripts whose expression increases during prion disease and remains unchanged during cuprizone-triggered neuropathology.  In this study, expression profiles from the brains of mice preclinically and clinically infected with Rocky Mountain Laboratory (RML) mouse-adapted scrapie agent and age-matched controls were profiled using Affymetrix gene arrays.  In total, 164 genes were differentially regulated during prion infection.  Eighty-three of these transcripts have been previously undescribed as differentially regulated during prion disease.  A 0.4% cuprizone diet was utilized as a control for comparative expression profiling.  Cuprizone treatment induced spongiosis and astrocyte proliferation as indicated by glial fibrillary acidic protein (Gfap) transcriptional activation and immunohistochemistry.  Gene expression profiles from brain tissue obtained from cuprizone-treated mice identified 307 differentially regulated transcript changes.  After comparative analysis, 17 transcripts unaffected by cuprizone treatment but increasing in expression from preclinical to clinical prion infection were identified.  Here we describe the novel use of the prion disease mimetic, cuprizone, to control for cell population changes in the brain during prion infection.

Authors

Laura R. Moody

Program in Cellular and Molecular Biology, University of Wisconsin, Madison, Wisconsin, USA; Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin, USA

Allen J. Herbst

Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin, USA; Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, Alberta, Canada

Han Sang Yoo

College of Veterinary Medicine, KRF Zoonotic Disease Priority Research Institute and BK21 for Veterinary Science, Seoul National University, Seoul, Korea

Joshua P. Vanderloo

Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin, USA

Judd M. Aiken Corresponding author: jmaiken@ualberta.ca

1Program in Cellular and Molecular Biology, University of Wisconsin, Madison, Wisconsin, USA; Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin, USA; Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, Alberta, Canada

This is an open-access article

 Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.