Gene expression profiling of scrapie-infected brain tissue

Riemer, Constanze; Neidhold, Sabine; Burwinkel, Michael; Schwarz, Anja; Schultz, Julia; Krätzschmar, Jörn; Mönning, Ursula; Baier, Michael

doi:10.1016/j.bbrc.2004.08.124

Cited by 105 publications

(116 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Analysis of differential gene expression in prion-infected mice suggests many perturbations in cholesterol homeostasis in addition to upregulation of Abca1 (Riemer et al, 2004;Xiang et al, 2004Xiang et al, , 2007) (D. Hwang and others, unpublished results). To mention only a few examples, the sterol-O-acyltransferase 1 gene (Soat1) that encodes acylcoenzyme A : cholesterol acyltransferase (ACAT) is overexpressed in prion-infected mice.…”

Section: Discussionmentioning

confidence: 98%

“…Expression of the apolipoprotein genes Apod and Apoe also increases in parallel with Abca1 during the course of infection. LDL receptor mRNA is reduced in scrapie-infected mouse brain (Riemer et al, 2004). The mechanism by which prion infection alters cholesterol homeostasis is not known, but may be related to alterations in recycling of PrP, synaptic membrane degeneration or to cellular stress responses.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Cholesterol transporter ATP-binding cassette A1 (ABCA1) is elevated in prion disease and affects PrPC and PrPSc concentrations in cultured cells

Kumar

McClain

Young

et al. 2008

Journal of General Virology

View full text Add to dashboard Cite

Prion diseases are transmissible neurodegenerative disorders of prion protein (PrP) conformation. Prion replication by conversion of benign PrP C isoforms into disease-specific PrP Sc isoforms is intimately involved in prion disease pathogenesis and may be initiated in cholesterol-rich caveolae-like domains (CLD). Concentrations of the cholesterol transporter ATP-binding cassette A1 protein (ABCA1) are elevated in pre-clinical scrapie prion-infected mice and in prion-infected cells in vitro. Elevation of ABCA1 in prion-infected brain is not a direct consequence of local PrP Sc accumulation, indeed levels of ABCA1 are comparable in brain regions that differ dramatically in the amount of PrP Sc . Similarly, ABCA1 concentrations are identical in normal mice, transgenic mice overexpressing PrP and PrP knockout mice. In contrast, PrP C and PrP Sc levels, but not Prnp mRNA, were increased by overexpression of ABCA1 in N2a neuroblastoma cells and scrapie prion-infected N2a cells (ScN2a). Conversely, RNAi-mediated knock down of Abca1 expression decreased the concentrations of PrP C in N2a cells and of PrP Sc in ScN2a cells. These results suggest that ABCA1's effects on PrP C levels are post-translational and may reflect an increase in of PrP C stability, mediated either indirectly by increasing membrane cholesterol and CLD formation or by other functions of ABCA1. The increased supply of PrP C available for conversion would lead to increased PrP Sc formation. INTRODUCTIONCreutzfeldt-Jakob disease and Kuru in humans, bovine spongiform encephalopathy, scrapie in sheep and chronic wasting disease in cervids are members of the group of neurodegenerative protein folding disorders caused by prions (Prusiner, 1998). Prion replication involves conversion of benign cellular isoforms, designated PrP C , into disease-specific isoforms, designated PrP Sc . The cellular site for prion replication is not well defined; in vitro and in vivo studies suggest that it takes place at the plasma membrane, where the initial interaction between endogenous glycosylphosphatidylinositol (GPI)-anchored PrP C and exogenous PrP Sc occurs, and in endosomal compartments (Campana et al., 2005;Harris, 1999). Substantial evidence suggests that PrP Sc generation takes place in cholesterol-rich, detergent insoluble membrane domains that are identified by various names, including caveolae-like domains (CLD), detergent resistant membranes and lipid rafts (Caughey & Raymond, 1991;Kaneko et al., 1997; Sarnataro et al., 2004;Vey et al., 1996). Cholesterol is required for PrP C cellsurface expression and stability (Caughey & Raymond, 1991;Gilch et al., 2006;Kaneko et al., 1997; Sarnataro et al., 2004) and pharmacological treatments that lower cellular cholesterol reduce PrP Sc generation and prolong prion incubation time (Bate et al., 2004;Gilch et al., 2006;Marella et al., 2002; Taraboulos et al., 1995).Genes involved in cholesterol metabolism and transport are consistently found among differentially expressed genes (DEGs) in prion-infected mice and cell line...

show abstract

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Cholesterol transporter ATP-binding cassette A1 (ABCA1) is elevated in prion disease and affects PrPC and PrPSc concentrations in cultured cells

Kumar

McClain

Young

et al. 2008

Journal of General Virology

View full text Add to dashboard Cite

show abstract

“…Finally, we want to emphasize that although we exclusively discuss our approach for dealing MEA data, this technique is readily applicable to many other types of data including gene microarrays (Riemer et al, 2004) and brain imaging (Todd and Marois, 2004) where, again, effects may be sparse across a large sample of loci.…”

Section: Discussionmentioning

confidence: 99%

Applications of multi-variate analysis of variance (MANOVA) to multi-electrode array electrophysiology data

Horton

Bonny

Nicol

et al. 2005

Journal of Neuroscience Methods

View full text Add to dashboard Cite

We have developed an adaptation of multi-variate analysis of variance (MANOVA) to analyze statistically both local and global patterns of multi-electrode array (MEA) electrophysiology data where the activities of many (typically >100) neurons have been recorded simultaneously. Whereas simple application of standard MANOVA techniques prohibits extraction of useful information in this kind of data, our new approach, MEANOVA (=MEA + MANOVA), allows a more useful and powerful approach to analyze such complex neurophysiological data. The MEANOVA test enables the detection of the "hot-spots" in the MEA data and has been validated using recordings from the rat olfactory bulb. To further validate the power of this approach, we have also applied the MEANOVA test to data obtained from a simple computational network model. This MEANOVA software and other useful statistical methods for MEA data can be downloaded from http://www.sussex.ac.uk/Users/pmh20.

show abstract

“…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.…”

Section: Preclinical Ca1 Microrna Profilesmentioning

confidence: 99%