Identification of central nervous system genes involved in the host response to the scrapie agent during preclinical and clinical infection

Abstract

Genes that are expressed differentially in the central nervous system of mice during infection with mouse-adapted scrapie agents were identified in this study. cDNA microarrays were used to examine gene-expression profiles at early, middle (preclinical) and late (clinical) time points after inoculation. A number of genes that showed significant changes in expression during the clinical stage of disease were identified. Of these, 138 were upregulated and 20 were downregulated. A smaller number of genes showed differential expression at the early and middle stages of the disease time course. These genes are interesting, as they may reflect biological processes that are involved in the molecular pathogenesis of the prion agent. At present, little is known about the early events in the disease process that trigger neurodegeneration. Perhaps most interestingly, one group of genes that exhibited decreased expression in all tested stages of the disease was identified in this study. This cluster included four transcripts representing haematopoietic system-related genes, which suggests that the haematopoietic system is involved in the disease process from an early stage.

Prion Infection of Mouse Brain Reveals Multiple New Upregulated Genes Involved in Neuroinflammation or Signal Transduction

“…Various high-throughput techniques, such as microarray expression profiling (11)(12)(13)(14)(15)(16)(17)(18)(19) and quantitative bead-based suspension array systems (3,20,21), have allowed elucidation of transcriptional and protein changes in brains of prion-infected mice relative to controls. These studies supported the notion that prion diseases have a neuroinflammatory component that may play a critical role in neurodegeneration (22), with increases in numerous cytokines and chemokines, such as interleukin-1␣ (IL-1␣) and IL-1␤, IL-12p40, tumor necrosis factor (TNF), CCL2 to CCL6, and CXCL10 in the brains of mice with clinical disease.…”

Transcriptional Changes in the Brains of Cattle Orally Infected with the Bovine Spongiform Encephalopathy Agent Precede Detection of Infectivity

“…The correlation between BSE pathogenesis and the transcriptional activities of genes is however not explored in any detail. Gene expression profiling studies of mice with scrapie have shown that these studies can provide valuable insights in the possible pathomechanisms of the disease (5,25,27,29,36,37).…”

Microdissection and transcriptional profiling

“…As noted, some of the most prominent incipient prion-related changes from whole tissue analyses (i.e., inflammation, cell adhesion, cell proliferation, energy metabolism, pattern recognition receptors and leukocyte extravasation) [27][28][29][30][64][65][66] were largely absent from the microdissected neuronal material or relegated to the later time-points when disease coincided with the significant infiltration of immune cells into the dissection field. This means that we can start to differentiate between temporal changes in neurons and the interplay with other cells that make up the brain tissue milieu.…”