title: Gene expression profiling of brains from bovine spongiform encephalopathy (BSE)-infected cynomolgus macaques.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.forename: Maura
authors.initials: M
authors.lastname: Barbisin
authors.forename: Silvia
authors.initials: S
authors.lastname: Vanni
authors.forename: Ann-Christin
authors.initials: AC
authors.lastname: Schmädicke
authors.forename: Judith
authors.initials: J
authors.lastname: Montag
authors.forename: Dirk
authors.initials: D
authors.lastname: Motzkus
authors.forename: Lennart
authors.initials: L
authors.lastname: Opitz
authors.forename: Gabriela
authors.initials: G
authors.lastname: Salinas-Riester
authors.affiliation: Department of Neuroscience, Scuola Internazionale Superiore di Studi Avanzati (SISSA), Via Bonomea 265, 34136 Trieste, Italy. legname@sissa.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Legname
mesh_terms: D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D002417:Cattle; D016643:Encephalopathy, Bovine Spongiform / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods* / Q000662:veterinary*; D007113:Immunity, Innate; D008055:Lipids / Q000502:physiology; D008252:Macaca fascicularis; D008969:Molecular Sequence Data; D010100:Oxygen / Q000378:metabolism
chemical_list: D008055:Lipids; D010100:Oxygen