Gene Expression in the Medulla Following Oral Infection of Cattle with Bovine Spongiform Encephalopathy

Abstract

The identification of variations in gene expression in response to bovine spongiform encephalopathy (BSE) may help to elucidate the mechanisms of neuropathology and prion replication and discover biomarkers for disease. In this study, genes that are differentially expressed in the caudal medulla tissues of animals infected with different doses of PrP(BSE) at 12 and 45 mo post infection were compared using array containing 24,000 oligonucleotide probes. Data analysis identified 966 differentially expressed (DE) genes between control and infected animals. Genes identified in at least two of four experiments (control versus 1-g infected animals at 12 and 45-mo; control versus 100-g infected animals at 12 and 45 mo) were considered to be the genes that may be associated with BSE disease. From the 176 DE genes associated with BSE, 84 had functions described in the Gene Ontology (GO) database. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of 14 genes revealed that prion infection may cause dysfunction of several different networks, including extracellular matrix (ECM), cell adhesion, neuroactive ligand-receptor interaction, complement and coagulation cascades, MAPK signaling, neurodegenerative disorder, SNARE interactions in vesicular transport, and the transforming growth factor (TGF) beta signaling pathways. The identification of DE genes will contribute to a better understanding of the molecular mechanisms of neuropathology in bovine species. Additional studies on larger number of animals are in progress in our laboratory to investigate the roles of these DE genes in pathogenesis of BSE.

Functional Genomics Approach for Identification of Molecular Processes Underlying Neurodegenerative Disorders in Prion Diseases

“…In cattle, orally infected with BSE agent (12 and 45 months post-infection), 101 DE genes in Peyer’s patch tissues [52] and 176 DE genes in medulla [53, 54] have been identified. These genes are mainly associated with the synapse function (e.g., tachykinin, synuclein, neuropeptide Y, cocaine, amphetamine-responsive transcript, and synaptosomal-associated protein 25 kDa); calcium ion regulation (e.g., parvalbumin, visinin-like, and cadherin); immune and inflammatory response (major histocompatibility complex (MHC) class II), and apoptosis (cholinergic receptor).…”

“…This study identified 190 DE transcripts from different pathways including neuroactive ligand–receptor interaction, regulation of the actin cytoskeleton, focal adhesion, SNARE interactions in vesicular transport, T-cell receptor signaling, calcium signaling, TGF-beta signaling, and MAPK signaling. Inaddition, the Tag profiling was successful in identifying additional pathways like ErbB signaling, the T cell receptor, the Wnt signaling, antigen processing, cytokine-cytokine receptor interaction, Gap junction, and the PPAR signaling as compared to the previous microarray studies on BSE-infected medulla tissues [53, 55]. The common DE genes detected in all these studies [52-55, 65] on cattle were: S100 calcium binding and Calmodulin; Prolactin-related protein; GTPase, IMAP family member, Histocompatibility complex, class II, Metallopeptidase and Myosin, Glutathione S transferase A, Aldo-Keto reductase family and Nuclear receptor subfamily group H.…”

Prion protein function and the disturbance of early embryonic development in zebrafish

“…Detected changes in gene expression would also be expected to vary with the species examined. The investigation of the transcriptomes of scrapie infected Peyer's patches of sheep 17,18 and global approaches to caudal medulla tissues from cattle infected with bovine spongiform encephalopathy 19 have shown that 100-200 genes are significantly up-or downregulated. These results revealed that prion infection may cause dysfunction of several molecular networks, including extracellular matrix, cell adhesion, neuroactive ligand-receptor interaction, complement and coagulation cascades, MAPK signaling, neurodegenerative disorder, SNARE interactions in vesicular transport, and the transforming growth factor beta signaling pathways.…”

Central nervous system gene expression changes in a transgenic mouse model for bovine spongiform encephalopathy

“…Several studies have been published on gene expression analysis concerning scrapie [12,18,19] but this kind of information about BSE has only been recently available [10,13-15,20]. In this paper a dynamical study of the evolution of the disease was performed by an oligonucleotide microarray genome wide gene expression analysis done on a well characterized transgenic mouse model of BSE on different time points of the disease.…”