Quantitative assessment of the astrocytic response in natural scrapie of sheep

Georgsson, Guðmundur; Gísladóttir, E.; Árnadóttir, Steinunn

doi:10.1016/s0021-9975(08)80287-3

Cited by 30 publications

(13 citation statements)

References 15 publications

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“…We used the GAMM v1.4 software [41] to perform a Mixed Model Analysis using a Bayesian approach that allowed the establishment of associations between gene expression data and prion deposition, gliosis and spongiosis. The spongiosis, PrP Sc deposits and generalized reactive gliosis observed in the medulla oblongatas of scrapie-affected animals in the present study were in accordance with previous descriptions of classical scrapie [31], [70], [71], [72], [73] and support the hypothesis that PrP Sc deposition elicits a responsive glial cell proliferation and the appearance of spongiotic lesions [15], [74], [75], [76]. The increase of GFAP in affected animals was in accordance with the microarray experiment results, in which the GFAP gene was upregulated in scrapie medullae with a 1.7-fold change (data not shown in Table S1 because only genes with a FC>2 are represented).…”

Section: Discussionsupporting

confidence: 93%

Gene Expression Profiling and Association with Prion-Related Lesions in the Medulla Oblongata of Symptomatic Natural Scrapie Animals

Filali

Martín-Burriel

Harders³

et al. 2011

PLoS ONE

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The pathogenesis of natural scrapie and other prion diseases remains unclear. Examining transcriptome variations in infected versus control animals may highlight new genes potentially involved in some of the molecular mechanisms of prion-induced pathology. The aim of this work was to identify disease-associated alterations in the gene expression profiles of the caudal medulla oblongata (MO) in sheep presenting the symptomatic phase of natural scrapie. The gene expression patterns in the MO from 7 sheep that had been naturally infected with scrapie were compared with 6 controls using a Central Veterinary Institute (CVI) custom designed 4×44K microarray. The microarray consisted of a probe set on the previously sequenced ovine tissue library by CVI and was supplemented with all of the Ovis aries transcripts that are currently publicly available. Over 350 probe sets displayed greater than 2-fold changes in expression. We identified 148 genes from these probes, many of which encode proteins that are involved in the immune response, ion transport, cell adhesion, and transcription. Our results confirm previously published gene expression changes that were observed in murine models with induced scrapie. Moreover, we have identified new genes that exhibit differential expression in scrapie and could be involved in prion neuropathology. Finally, we have investigated the relationship between gene expression profiles and the appearance of the main scrapie-related lesions, including prion protein deposition, gliosis and spongiosis. In this context, the potential impacts of these gene expression changes in the MO on scrapie development are discussed.

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Section: Discussionsupporting

confidence: 93%

Gene Expression Profiling and Association with Prion-Related Lesions in the Medulla Oblongata of Symptomatic Natural Scrapie Animals

Filali

Martín-Burriel

Harders³

et al. 2011

PLoS ONE

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“…The transcriptional accumulation of glial fibrillary acidic protein (GFAP), a specific marker for astrocytes, has also been observed. GFAP and its mRNAs are overexpressed in both natural and experimental scrapie (Dormont et al, 1981 ;Georgsson et al, 1993 ;Lazarini et al, 1994 ;Mackenzie, 1983).…”

Section: Introductionmentioning

confidence: 99%

MS-8209, a water-soluble amphotericin B derivative, affects both scrapie agent replication and PrPres accumulation in Syrian hamster scrapie.

Adjou

Demaimay

Deslys

et al. 1999

Journal of General Virology

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Amphotericin B (AmB) has been shown to delay hamster scrapie. Infectivity studies have been performed previously using AmB in order to understand the relationship between the accumulation of an abnormal isoform (PrPres) of the prion protein and 263K scrapie agent replication in the brain. The first study reported that AmB had no effect upon agent replication, although it delayed the development of both clinical signs and PrPres accumulation. However, subsequent experiments using the same model showed a significant effect both on agent replication and PrPres accumulation early in infection. This fundamental discrepancy was assumed to be linked to differences in experimental protocols. In order to unravel the issue, a new experiment has been performed encompassing different protocols and using an AmB derivative, MS-8209, that can be used at higher doses because of its lower toxicity. The findings of this study exclude the suspected differences in the protocols as the reason for previous conflicting results, and suggest strongly that these discrepancies were due to a low dose of AmB causing a ' threshold effect'. Overall, this study indicates that, in this model, PrPres cannot be dissociated from infectivity by polyene antibiotics.

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“…7 The most widely accepted histologic lesion is astrocytosis and vacuolation in neuronal cells, leading to the classification of the disease as a spongiform encephalopathy. An astroglial reaction is a common histologic feature in natural 1,2,6 and in experimental 12 scrapie. Astrocytes are a target for the scrapie agent in the early pathogenesis of the disease.…”

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confidence: 99%

Immunohistochemical Detection of Scrapie Prion Proteins in Clinically Normal Sheep in Pennsylvania

Kim

O’Rourke²,

Walter

et al. 2001

J VET Diagn Invest

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Abstract. Following diagnosis of scrapie in a clinically suspect Suffolk sheep, 7 clinically normal flockmates were purchased by the Pennsylvania Department of Agriculture to determine their scrapie status using an immunohistochemical procedure. Two of the 7 euthanized healthy sheep had positive immunohistochemical staining of the prion protein of scrapie (PrP-Sc) in their brains, nictitating membranes, and tonsils. The PrP-Sc was localized in the areas of the brain where, histopathologically, there was neurodegeneration and astrocytosis. The PrP-Sc occurred within germinal centers of the affected nictitating membranes and tonsils and was located in the cytoplasm of the dendrite-like cells, lymphoid cells, and macrophages. These results confirm that immunohistochemical examination of the nictitating membrane can be used as a screen for the presence of scrapie infection in clinically normal sheep at a capable veterinary diagnostic laboratory. In sheep with a PrP-Sc-positive nictitating membrane, the diagnosis of scrapie should be confirmed by histopathology and immunohistochemical examination of the brain following necropsy. Following full validation, immunohistochemistry assays for detection of PrP-Sc in nictitating membrane lymphoid tissues can improve the effectiveness of the scrapie control and eradication program by allowing diagnosis of the disease in sheep before the appearance of clinical signs.Scrapie is the prototype of a heterogenous group of transmissible spongiform ecnephalopathies that occur in sheep, humans, cattle, cats, mink, and cervids and are characterized by the deposition of altered prion proteins in the central nervous system of affected individuals. 11 Scrapie in sheep has become a target of control measures and eradication programs. Crucial for the effectiveness of these measures is the detection of infected sheep. After infection, the disease has a particularly long incubation period during which the infected sheep may be able to transmit the disease to noninfected sheep. 3 Scrapie infectivity has been detected in the lymphoreticular system of sheep well before symptoms occur. 4,8,9 Detection of scrapie prion protein (PrP-Sc) in nictitating membrane or tonsil has been proposed as a diagnostic test for scrapie infection. 5,11,13 In this study at the Pennsylvania Veterinary Laboratory (PVL), an immunohistochemical procedure was applied to detection of PrP-Sc in clinically normal euthanized Suffolk sheep.A farm had 10 sheep in a flock that had been in existence since October 1991. A 7-year-old ewe from the farm was submitted to the PVL for necropsy on April 15, 1998. The ewe had shown signs of pruritis for a few months and had recently developed neurologic signs, including staggering, stumbling, and falling. The ewe was diagnosed as having scrapie by routine histopathology conducted at PVL and immunohistochemistry (IHC) of brain tissue conducted at the National Veterinary Services Laboratory (Ames, IA). On August 11, 1998, the Pennsylvania Department of Agriculture purchased the last 7 shee...

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Quantitative assessment of the astrocytic response in natural scrapie of sheep

Cited by 30 publications

References 15 publications

Gene Expression Profiling and Association with Prion-Related Lesions in the Medulla Oblongata of Symptomatic Natural Scrapie Animals

Gene Expression Profiling and Association with Prion-Related Lesions in the Medulla Oblongata of Symptomatic Natural Scrapie Animals

MS-8209, a water-soluble amphotericin B derivative, affects both scrapie agent replication and PrPres accumulation in Syrian hamster scrapie.

Immunohistochemical Detection of Scrapie Prion Proteins in Clinically Normal Sheep in Pennsylvania

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