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Veterinary Research 2008Atypical/Nor98 scrapie cases in sheep were diagnosed for the first time in Norway in 1998. They are now identified in small ruminants in most European countries and... (Review)
Review
Atypical/Nor98 scrapie cases in sheep were diagnosed for the first time in Norway in 1998. They are now identified in small ruminants in most European countries and represent an increasingly large proportion of the scrapie cases diagnosed in Europe. Atypical/Nor98 scrapie isolates have shown to be experimentally transmissible into transgenic mice and sheep but the properties of the TSE agent involved, like its biological and biochemical features, are so clearly distinct from the agent involved in classical scrapie that they have provided a challenging diagnostic for many years. No strain diversity has yet been identified among the atypical/Nor98 scrapie sample cases. The genetic predisposition of the sheep affected by atypical/Nor98 scrapie is almost inverted compared to classical scrapie, and the exact origin of this sporadic TSE strain is still speculative, but a spontaneous, non-contagious origin, like sporadic Creutzfeldt-Jakob disease in humans, can not be excluded. Further transmission and epidemiological studies are needed to better address this hypothesis.
Topics: Animals; Europe; Prions; Scrapie; Sheep
PubMed: 18187032
DOI: 10.1051/vetres:2007056 -
Revue Scientifique Et Technique... Apr 1997This paper reviews current knowledge on transmission of scrapie and bovine spongiform encephalopathy (BSE) by semen and embryos. In sheep, in particular, it is difficult... (Review)
Review
This paper reviews current knowledge on transmission of scrapie and bovine spongiform encephalopathy (BSE) by semen and embryos. In sheep, in particular, it is difficult to distinguish between the genetic transmission of susceptibility to scrapie and vertical transmission of the infection. Nevertheless, there is evidence that vertical transmission of infection does occur, probably across the placenta, but none to suggest a significant scrapie risk from semen. Two teams have studied scrapie transmission from experimentally infected sheep using embryo transfer. Whereas one team found no evidence for transmission, the results from the other team suggest that embryos, even after washing, might carry the disease into the offspring. In regard to goats, although genetic differences in susceptibility exist, they are much less obvious than in sheep. There is no evidence for vertical transmission or for transmission through semen and embryos. With regard to BSE, although it appears that genetic differences in susceptibility are absent or unimportant, some recent work does suggest that the disease may be passed from cow to calf. The route of transmission and stage or stages when this takes place are unclear, however. In conclusion, despite growing evidence to indicate that scrapie and BSE are unlikely to be transmitted through semen and embryos, more research is needed to confirm this. Furthermore, until all possibility of risk is ruled out, risk reduction methods must be considered, especially when semen and embryos are being imported into countries where the diseases do not exist.
Topics: Animals; Cattle; Embryo Transfer; Encephalopathy, Bovine Spongiform; Goat Diseases; Goats; Insemination, Artificial; Prions; Risk Factors; Scrapie; Semen; Sheep
PubMed: 9329121
DOI: 10.20506/rst.16.1.1016 -
TheScientificWorldJournal Oct 2001Transmissible spongiform encephalopathies are a group of invariably fatal neurodegenerative diseases. The infectious agent is termed prion and is thought to be composed...
Transmissible spongiform encephalopathies are a group of invariably fatal neurodegenerative diseases. The infectious agent is termed prion and is thought to be composed of a modified protein (PrP Sc or Pr PRES ), a protease-resistant conformer of the normal host-encoded membrane glycoprotein, PrP C. Bovine spongiform encephalopathy, scrapie of sheep, and Creutzfeldt-Jakob disease are among the most notable transmissible spongiform encephalopathies. Prions are most efficiently propagated trough intracerebral inoculation, yet the entry point of the infectious agent is often through peripheral sites like the gastrointestinal tract. The process by which prions invade the brain is termed neuroinvasion. We and others have speculated that, depending on the amount of infectious agent injected, the injection site, and the strain of prions employed, neuroinvasion can occur either directly via peripheral nerves or first through the lymphoreticular system and then via peripheral nerves.
Topics: Animals; Mice; Peripheral Nerves; PrPSc Proteins; Scrapie; Sympathetic Nervous System
PubMed: 12805849
DOI: 10.1100/tsw.2001.258 -
The molecular mechanisms of scrapie encephalopathy and relevance to human neurodegenerative disease.Canadian Journal of Veterinary Research... Jan 1990We have investigated alterations in the structure and function of nuclei isolated from normal and pathological brains in a number of neurodegenerative diseases including... (Review)
Review
We have investigated alterations in the structure and function of nuclei isolated from normal and pathological brains in a number of neurodegenerative diseases including scrapie and Alzheimer's disease. Here we summarize both general and specific changes in chromatin structure, gene expression, and neuropathological features for each encephalopathy and compare them in terms of their molecular biological similarities and differences. While both scrapie and Alzheimer's disease share a number of common alterations in genomic organization and gene activity during the pathogenic process, each neurological disease appears to operate on fundamentally different mechanisms.
Topics: Alzheimer Disease; Animals; Humans; Scrapie
PubMed: 2407330
DOI: No ID Found -
Cells Sep 2022Mitochondrial dynamics continually maintain cell survival and bioenergetics through mitochondrial quality control processes (fission, fusion, and mitophagy). Aberrant...
Mitochondrial dynamics continually maintain cell survival and bioenergetics through mitochondrial quality control processes (fission, fusion, and mitophagy). Aberrant mitochondrial quality control has been implicated in the pathogenic mechanism of various human diseases, including cancer, cardiac dysfunction, and neurological disorders, such as Alzheimer's disease, Parkinson's disease, and prion disease. However, the mitochondrial dysfunction-mediated neuropathological mechanisms in prion disease are still uncertain. Here, we used both in vitro and in vivo scrapie-infected models to investigate the involvement of mitochondrial quality control in prion pathogenesis. We found that scrapie infection led to the induction of mitochondrial reactive oxygen species (mtROS) and the loss of mitochondrial membrane potential (ΔΨm), resulting in enhanced phosphorylation of dynamin-related protein 1 (Drp1) at Ser616 and its subsequent translocation to the mitochondria, which was followed by excessive mitophagy. We also confirmed decreased expression levels of mitochondrial oxidative phosphorylation (OXPHOS) complexes and reduced ATP production by scrapie infection. In addition, scrapie-infection-induced aberrant mitochondrial fission and mitophagy led to increased apoptotic signaling, as evidenced by caspase 3 activation and poly (ADP-ribose) polymerase cleavage. These results suggest that scrapie infection induced mitochondrial dysfunction via impaired mitochondrial quality control processes followed by neuronal cell death, which may have an important role in the neuropathogenesis of prion diseases.
Topics: Animals; Humans; Mice; Mitochondria; Mitochondrial Dynamics; Mitophagy; Neurons; Prion Diseases; Prions; Scrapie
PubMed: 36078152
DOI: 10.3390/cells11172744 -
Veterinary Research 2007The aim of this study was to analyze the epidemiology and prion protein (PrP) genetics in scrapie-affected sheep flocks in Germany. For this purpose, 224 German scrapie...
The aim of this study was to analyze the epidemiology and prion protein (PrP) genetics in scrapie-affected sheep flocks in Germany. For this purpose, 224 German scrapie cases in sheep diagnosed between January 2002 and February 2006 were classified as classical or atypical scrapie and the amino acids at codons 136, 141, 154 and 171 were determined. Likewise, representative numbers of flock mates were genotyped. Significant epidemiological differences were observed between classical and atypical scrapie cases in regard to the numbers of scrapie-affected sheep within a flock, the sizes of flocks with only a single scrapie-positive sheep or more than one scrapie-positive sheep and the age distribution of the scrapie-positive sheep. Sheep with the ARQ/ARQ genotype had by far the highest risk for acquiring classical scrapie, but the risk for atypical scrapie was the highest for sheep carrying phenylalanine (F) at position 141 (AF(141)RQ) and/or the AHQ haplotype. However, atypical scrapie also occurred with a notable frequency in sheep with the PrP haplotypes ARR and/or ARQ in combination with Leucine at position 141 (AL(141)RQ). Furthermore, six atypical scrapie-positive sheep carried the PrP genotype ARR/ARR. The high proportion of sheep flocks affected by atypical scrapie underscores the importance of this scrapie type.
Topics: Animals; Genetic Variation; Genotype; Germany; PrPSc Proteins; Scrapie; Sheep
PubMed: 17156738
DOI: 10.1051/vetres:2006046 -
Scientific Reports Jun 2021To understand the possible role of mixed-prion infections in disease presentation, the current study reports the co-infection of sheep with bovine spongiform...
To understand the possible role of mixed-prion infections in disease presentation, the current study reports the co-infection of sheep with bovine spongiform encephalopathy (BSE) and scrapie. The bovine BSE agent was inoculated subcutaneously into sheep with ARQ/ARQ or VRQ/ARQ PRNP genotypes either at the same time as subcutaneous challenge with scrapie, or three months later. In addition, VRQ/VRQ sheep naturally infected with scrapie after being born into a scrapie-affected flock were challenged subcutaneously with BSE at eight or twenty one months-of-age. Sheep were analysed by incubation period/attack rate, and western blot of brain tissue determined the presence of BSE or scrapie-like PrP. Serial protein misfolding cyclic amplification (sPMCA) that can detect very low levels of BSE in the presence of an excess of scrapie agent was also applied to brain and lymphoreticular tissue. For VRQ/ARQ sheep challenged with mixed infections, scrapie-like incubation periods were produced, and no BSE agent was detected. However, whilst ARQ/ARQ sheep developed disease with BSE-like incubation periods, some animals had a dominant scrapie western blot phenotype in brain, but BSE was detected in these sheep by sPMCA. In addition, VRQ/VRQ animals challenged with BSE after natural exposure to scrapie had scrapie-like incubation periods and dominant scrapie PrP in brain, but one sheep had BSE detectable by sPMCA in the brain. Overall, the study demonstrates for the first time that for scrapie/BSE mixed infections, VRQ/ARQ sheep with experimental scrapie did not propagate BSE but VRQ/VRQ sheep with natural scrapie could propagate low levels of BSE, and whilst BSE readily propagated in ARQ/ARQ sheep it was not always the dominant PrP strain in brain tissue. Indeed, for several animals, a dominant scrapie biochemical phenotype in brain did not preclude the presence of BSE prion.
Topics: Animals; Brain; Cattle; Cattle Diseases; Coinfection; Encephalopathy, Bovine Spongiform; Genotype; Phenotype; Prion Proteins; Scrapie; Sheep; Sheep Diseases
PubMed: 34099797
DOI: 10.1038/s41598-021-91397-8 -
Veterinary Research 2008Classical scrapie has proved to be a notoriously difficult disease to control due to a poor understanding of its natural history. The recognition of disease risk linkage... (Review)
Review
Classical scrapie has proved to be a notoriously difficult disease to control due to a poor understanding of its natural history. The recognition of disease risk linkage to PrP genotype has offered the prospect of a disease control strategy, viz. genotyping and selective breeding, novel to veterinary medicine when first considered in the 1990s. The UK Spongiform Encephalopathy Advisory Committee recommended the exploitation of this approach in a voluntary, national programme to control classical scrapie and protect the public against food-borne exposure to bovine spongiform encephalopathy, should the national flock have been exposed via contaminated feed. The National Scrapie Plan for Great Britain was launched in 2001 and uptake has been widespread throughout the purebreeding sector of the sheep industry, with membership peaking at over 12 000 flocks in 2006. A total of 700 000 rams from 90 breeds have been genotyped. A comparison of ram lambs born in 2002 with those in 2006 shows evident changes in PrP genotype frequencies which are predicted to be associated with a reduction in disease risk. Various concerns have been raised regarding possible unintended consequences of widespread selection on PrP genotype, including impacts on other performance traits and possible effects on inbreeding and genetic diversity. To date, these concerns appear to be unfounded, as no consistent associations have been found with performance traits, nor are there likely to be any detectable impacts on inbreeding in mainstream breeds. Currently, semen banks have been implemented in Great Britain to store samples from animals of all common PrP genotypes, should these genotypes be required in the future. Various strategies to minimise future disease risks are discussed in the paper.
Topics: Animals; Breeding; Prions; Scrapie; Selection, Genetic; Sheep; United Kingdom
PubMed: 18258168
DOI: 10.1051/vetres:2007064 -
Brain Pathology (Zurich, Switzerland) Jul 1998The human prion diseases are fatal neurodegenerative maladies that may present as sporadic, genetic, or infectious illnesses. The sporadic form is called... (Review)
Review
The human prion diseases are fatal neurodegenerative maladies that may present as sporadic, genetic, or infectious illnesses. The sporadic form is called Creutzfeldt-Jakob disease (CJD) while the inherited disorders are called familial (f) CJD, Gerstmann-Straussler-Scheinker (GSS) disease and fatal familial insomnia (FFI). Prions are transmissible particles that are devoid of nucleic acid and seem to be composed exclusively of a modified protein (PrPSc). The normal, cellular PrP (PrPC) is converted into PrPSc through a posttranslational process during which it acquires a high beta-sheet content. In fCJD, GSS, and FFI, mutations in the PrP gene located on the short arm of chromosome 20 are the cause of disease. Considerable evidence argues that the prion diseases are disorders of protein conformation.
Topics: Animals; Creutzfeldt-Jakob Syndrome; Encephalopathy, Bovine Spongiform; Humans; Models, Molecular; Prion Diseases; Prions; Scrapie
PubMed: 9669700
DOI: 10.1111/j.1750-3639.1998.tb00171.x -
Revue Scientifique Et Technique... Apr 2003Bovine spongiform encephalopathy (BSE) in sheep has not been identified under natural conditions at the time of writing and remains a hypothetical issue. However,... (Review)
Review
Bovine spongiform encephalopathy (BSE) in sheep has not been identified under natural conditions at the time of writing and remains a hypothetical issue. However, rumours about the possible finding of a BSE-like isolate in sheep have led to great unrest within the sheep industry, among the general public and within governmental and regulatory bodies. The difficulties of implementing a proper risk assessment and pre-emptive measures, in the absence of a confirmed case, are described. The authors attempt to list what is known about experimental BSE in sheep, the distribution of infectivity in the host, some aspects of risk assessment and management and the most promising methods for differentiating BSE from scrapie in the same host. As for the latter, new and promising methods are being developed and appear suitable for initial screening of isolates of transmissible spongiform encephalopathies, but in the absence of proper validation, use of the 'classical' strain-typing in a mouse panel is still indicated.
Topics: Animal Feed; Animal Husbandry; Animals; Cattle; Diagnosis, Differential; Encephalopathy, Bovine Spongiform; Genotype; Goat Diseases; Goats; Humans; Mice; Prions; Risk Assessment; Risk Factors; Scrapie; Sheep; Sheep Diseases; Zoonoses
PubMed: 12793775
DOI: 10.20506/rst.22.1.1387