Gene expression profiling of brains from bovine spongiform encephalopathy (BSE)-infected cynomolgus macaques
- Equal contributors
1 Department of Neuroscience, Scuola Internazionale Superiore di Studi Avanzati (SISSA), Via Bonomea 265, 34136 Trieste, Italy
2 Unit of Infection Models, German Primate Center, Kellnerweg 4, 37077 Göttingen, Germany
3 Microarray Core Facility, University Medical Center Göttingen, Justus-von-Liebig-Weg 11, 37077 Göttingen, Germany
4 Molecular and Cell Physiology, Hannover Medical School, Carl-Neuberg Str. 1, D-30625 Hannover, Germany
BMC Genomics 2014, 15:434 doi:10.1186/1471-2164-15-434Published: 5 June 2014
Prion diseases are fatal neurodegenerative disorders whose pathogenesis mechanisms are not fully understood. In this context, the analysis of gene expression alterations occurring in prion-infected animals represents a powerful tool that may contribute to unravel the molecular basis of prion diseases and therefore discover novel potential targets for diagnosis and therapeutics. Here we present the first large-scale transcriptional profiling of brains from BSE-infected cynomolgus macaques, which are an excellent model for human prion disorders.
The study was conducted using the GeneChip® Rhesus Macaque Genome Array and revealed 300 transcripts with expression changes greater than twofold. Among these, the bioinformatics analysis identified 86 genes with known functions, most of which are involved in cellular development, cell death and survival, lipid homeostasis, and acute phase response signaling. RT-qPCR was performed on selected gene transcripts in order to validate the differential expression in infected animals versus controls. The results obtained with the microarray technology were confirmed and a gene signature was identified. In brief, HBB and HBA2 were down-regulated in infected macaques, whereas TTR, APOC1 and SERPINA3 were up-regulated.
Some genes involved in oxygen or lipid transport and in innate immunity were found to be dysregulated in prion infected macaques. These genes are known to be involved in other neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. Our results may facilitate the identification of potential disease biomarkers for many neurodegenerative diseases.