Whole transcriptome analysis in brains from BSE-infected macaques

Prion diseases are neurodegenerative disorders that affect both humans and animals. The molecular mechanisms underlying prion replication and subsequent degeneration of the central nervous system are still poorly understood. In an attempt to identify molecules that are putatively involved in the etiology of these diseases, we conducted a whole transcriptome analysis with brain tissue from BSE-infected and uninfected cynomolgus macaques (M. fascicularis). Total RNA from the gyrus frontalis region of seven BSE-infected and five noninfected control macaques was isolated. The integrity of the RNA was assessed using an Agilent 2100 Bioanalyzer. The RNA was reverse-transcribed, labeled and analyzed on an GeneChip® Rhesus Macaque Genome Array (Affymetrix) containing 52,024 Macaca mulatta probe sets to monitor the gene expression of approximately 47,000 transcripts. Bioinformatic analysis revealed that about 100 transcripts were significantly up-or down-regulated more than twofold. Beside others, we found up-regulation of α1-antichymotrypsin, which has also been described in scrapie-infected mice and Alzheimer’s disease. We are currently validating the most interesting candidates using quantitative RT-PCR. Our approach may help to identify genes that are crucial to prion disease processes and may become potential targets for diagnostic and therapeutic strategies.