Comparison of Brain PrPd Distribution in Ovine BSE and Scrapie

2011 ◽  
Vol 48 (6) ◽  
pp. 1101-1108 ◽  
Author(s):  
S. Lezmi ◽  
T. Seuberlich ◽  
A. Oevermann ◽  
T. Baron ◽  
A. Bencsik
Keyword(s):  
Frontal Cortex ◽  
Prion Diseases ◽  
Piriform Cortex ◽  
Small Ruminants ◽  
Infected Sheep ◽  
Spongiform Encephalopathy ◽  
Genotype Distribution ◽  
Prion Strains ◽  
Incubation Periods ◽  
The Brain

Scrapie and bovine spongiform encephalopathy (BSE) are both prion diseases affecting ruminants, and these diseases do not share the same public health concerns. Surveillance of the BSE agent in small ruminants has been a great challenge, and the recent identification of diverse prion diseases in ruminants has led to the development of new methods for strain typing. In our study, using immunohistochemistry (IHC), we assessed the distribution of PrPd in the brains of 2 experimentally BSE-infected sheep with the ARQ/ARQ genotype. Distribution of PrPd in the brain, from the spinal cord to the frontal cortex, was remarkably similar in the 2 sheep despite different inoculation routes and incubation periods. Comparatively, overall PrPd brain distribution, evaluated by IHC, in 19 scrapie cases with the ARQ/ARQ, ARQ/VRQ, and VRQ/VRQ genotypes, in some cases showed similarities to the experimentally BSE-infected sheep. There was no exclusive neuroanatomical site with a characteristic and specific PrPd type of accumulation induced by the BSE agent. However, a detailed analysis of the topography, types, and intensity of PrPd deposits in the frontal cortex, striatum, piriform cortex, hippocampus, mesencephalon, and cerebellum allowed the BSE-affected sheep group to be distinguished from the 19 scrapie cases analyzed in our study. These results strengthen and emphasize the potential interest of PrPd brain mapping to help in identifying prion strains in small ruminants.

scholarly journals Detection and characterization of proteinase K-sensitive disease-related prion protein with thermolysin

2008 ◽  
Vol 416 (2) ◽  
pp. 297-305 ◽  
Author(s):  
Sabrina Cronier ◽  
Nathalie Gros ◽  
M. Howard Tattum ◽  
Graham S. Jackson ◽  
Anthony R. Clarke ◽  
...  
Keyword(s):  
Prion Protein ◽  
Prion Diseases ◽  
Rocky Mountain ◽  
Proteinase K ◽  
Spongiform Encephalopathy ◽  
Prion Strains ◽  
Human Counterpart ◽  
Jakob Disease ◽  
The Brain

Disease-related PrPSc [pathogenic PrP (prion protein)] is classically distinguished from its normal cellular precursor, PrPC(cellular PrP) by its detergent insolubility and partial resistance to proteolysis. Although molecular diagnosis of prion disease has historically relied upon detection of protease-resistant fragments of PrPSc using PK (proteinase K), it is now apparent that a substantial fraction of disease-related PrP is destroyed by this protease. Recently, thermolysin has been identified as a complementary tool to PK, permitting isolation of PrPSc in its full-length form. In the present study, we show that thermolysin can degrade PrPC while preserving both PK-sensitive and PK-resistant isoforms of disease-related PrP in both rodent and human prion strains. For mouse RML (Rocky Mountain Laboratory) prions, the majority of PK-sensitive disease-related PrP isoforms do not appear to contribute significantly to infectivity. In vCJD (variant Creutzfeldt–Jakob disease), the human counterpart of BSE (bovine spongiform encephalopathy), up to 90% of total PrP present in the brain resists degradation with thermolysin, whereas only ∼15% of this material resists digestion by PK. Detection of PK-sensitive isoforms of disease-related PrP using thermolysin should be useful for improving diagnostic sensitivity in human prion diseases.

scholarly journals PrP(d) accumulation in organs of ARQ/ARQ sheep experimentally infected with BSE by peripheral routes.

2006 ◽  
Vol 53 (2) ◽  
pp. 399-405 ◽  
Author(s):  
Stéphane Lezmi ◽  
Frédéric Ronzon ◽  
Anna Bencsik ◽  
Alexandre Bedin ◽  
Didier Calavas ◽  
...  
Keyword(s):  
Prion Protein ◽  
Peripheral Nerves ◽  
Clinical Symptoms ◽  
Prion Diseases ◽  
Small Ruminants ◽  
Brain Homogenate ◽  
Spongiform Encephalopathy ◽  
Post Inoculation ◽  
Muscle Types ◽  
Immunohistochemical Methods

To study the pathogenesis of bovine spongiform encephalopathy infection in small ruminants, two Lacaune sheep with the AA136RR154QQ171 and one with the AA136RR154RR171 genotype for the prion protein, were inoculated with a brain homogenate from a French cattle BSE case by peripheral routes. Sheep with the ARQ/ARQ genotype are considered as susceptible to prion diseases contrary to those with the ARR/ARR genotype. The accumulation of disease-associated prion protein (PrP(d)) was analysed by biochemical and immunohistochemical methods. No PrP(d) accumulation was detected in samples from the ARR/ARR sheep 2 years post inoculation. In the two ARQ/ARQ sheep that had scrapie-like clinical symptoms, PrP(d) was found in the central, sympathetic and enteric nervous systems and in lymphoid organs. Remarkably, PrP(d) was also detected in some muscle types as well as in all peripheral nerves that had not been reported previously thus revealing a widespread distribution of BSE-associated PrP(d) in sheep tissues.

scholarly journals Strain-Dependent Prion Infection in Mice Expressing Prion Protein with Deletion of Central Residues 91–106

2020 ◽  
Vol 21 (19) ◽  
pp. 7260
Author(s):  
Keiji Uchiyama ◽  
Hironori Miyata ◽  
Yoshitaka Yamaguchi ◽  
Morikazu Imamura ◽  
Mariya Okazaki ◽  
...  
Keyword(s):  
Prion Protein ◽  
Protein Misfolding ◽  
Prion Diseases ◽  
Cellular Prion Protein ◽  
Spongiform Encephalopathy ◽  
Dependent Manner ◽  
Prion Infection ◽  
Amplification Assay ◽  
The Brain ◽  
Strain Dependent

Conformational conversion of the cellular prion protein, PrPC, into the abnormally folded isoform, PrPSc, is a key pathogenic event in prion diseases. However, the exact conversion mechanism remains largely unknown. Transgenic mice expressing PrP with a deletion of the central residues 91–106 were generated in the absence of endogenous PrPC, designated Tg(PrP∆91–106)/Prnp0/0 mice and intracerebrally inoculated with various prions. Tg(PrP∆91–106)/Prnp0/0 mice were resistant to RML, 22L and FK-1 prions, neither producing PrPSc∆91–106 or prions in the brain nor developing disease after inoculation. However, they remained marginally susceptible to bovine spongiform encephalopathy (BSE) prions, developing disease after elongated incubation times and accumulating PrPSc∆91–106 and prions in the brain after inoculation with BSE prions. Recombinant PrP∆91-104 converted into PrPSc∆91–104 after incubation with BSE-PrPSc-prions but not with RML- and 22L–PrPSc-prions, in a protein misfolding cyclic amplification assay. However, digitonin and heparin stimulated the conversion of PrP∆91–104 into PrPSc∆91–104 even after incubation with RML- and 22L-PrPSc-prions. These results suggest that residues 91–106 or 91–104 of PrPC are crucially involved in prion pathogenesis in a strain-dependent manner and may play a similar role to digitonin and heparin in the conversion of PrPC into PrPSc.

scholarly journals Transmissible Spongiform Encephalopathies Affecting Humans

2013 ◽  
Vol 2013 ◽  
pp. 1-11
Author(s):  
Dudhatra G. B. ◽  
Avinash Kumar ◽  
Modi C. M. ◽  
Awale M. M. ◽  
Patel H. B. ◽  
...  
Keyword(s):  
Neurological Disease ◽  
Prion Diseases ◽  
Transmissible Spongiform Encephalopathies ◽  
Spongiform Encephalopathies ◽  
Neurologic Diseases ◽  
Abnormal Protein ◽  
Chain Reactions ◽  
Personality Changes ◽  
Incubation Periods ◽  
The Brain

Transmissible spongiform encephalopathies (TSEs) or prion diseases are group of rare and rapidly progressive fatal neurologic diseases. The agents responsible for human prion diseases are abnormal proteins or prion that can trigger chain reactions causing normal proteins in the brain to change to the abnormal protein. These abnormal proteins are resistant to enzymatic breakdown, and they accumulate in the brain, leading to damage. TSEs have long incubation periods followed by chronic neurological disease and fatal outcomes, have similar pathology limited to the CNS including convulsions, dementia, ataxia, and behavioral or personality changes, and are experimentally transmissible to some other species.

scholarly journals Classical and Atypical Scrapie in Sheep and Goats. Review on the Etiology, Genetic Factors, Pathogenesis, Diagnosis, and Control Measures of Both Diseases

Animals ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 691
Author(s):  
Cristina Acín ◽  
Rosa Bolea ◽  
Marta Monzón ◽  
Eva Monleón ◽  
Bernardino Moreno ◽  
...  
Keyword(s):  
Prion Protein ◽  
Genetic Factors ◽  
Prion Diseases ◽  
Transmissible Spongiform Encephalopathy ◽  
Fatal Outcome ◽  
Small Ruminants ◽  
Cellular Prion Protein ◽  
Spongiform Encephalopathy ◽  
Atypical Scrapie ◽  
Sheep And Goats

Prion diseases, such as scrapie, are neurodegenerative diseases with a fatal outcome, caused by a conformational change of the cellular prion protein (PrPC), originating with the pathogenic form (PrPSc). Classical scrapie in small ruminants is the paradigm of prion diseases, as it was the first transmissible spongiform encephalopathy (TSE) described and is the most studied. It is necessary to understand the etiological properties, the relevance of the transmission pathways, the infectivity of the tissues, and how we can improve the detection of the prion protein to encourage detection of the disease. The aim of this review is to perform an overview of classical and atypical scrapie disease in sheep and goats, detailing those special issues of the disease, such as genetic factors, diagnostic procedures, and surveillance approaches carried out in the European Union with the objective of controlling the dissemination of scrapie disease.

scholarly journals Neuropathology of Animal Prion Diseases

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 466
Author(s):  
Leonor Orge ◽  
Carla Lima ◽  
Carla Machado ◽  
Paula Tavares ◽  
Paula Mendonça ◽  
...  
Keyword(s):  
Prion Diseases ◽  
Clinical Signs ◽  
Small Ruminants ◽  
Neuronal Loss ◽  
Cellular Prion Protein ◽  
Brain Inflammation ◽  
Transmissible Spongiform Encephalopathies ◽  
Spongiform Encephalopathy ◽  
Spongiform Encephalopathies ◽  
Lesion Profile

Transmissible Spongiform Encephalopathies (TSEs) or prion diseases are a fatal group of infectious, inherited and spontaneous neurodegenerative diseases affecting human and animals. They are caused by the conversion of cellular prion protein (PrPC) into a misfolded pathological isoform (PrPSc or prion- proteinaceous infectious particle) that self-propagates by conformational conversion of PrPC. Yet by an unknown mechanism, PrPC can fold into different PrPSc conformers that may result in different prion strains that display specific disease phenotype (incubation time, clinical signs and lesion profile). Although the pathways for neurodegeneration as well as the involvement of brain inflammation in these diseases are not well understood, the spongiform changes, neuronal loss, gliosis and accumulation of PrPSc are the characteristic neuropathological lesions. Scrapie affecting small ruminants was the first identified TSE and has been considered the archetype of prion diseases, though atypical and new animal prion diseases continue to emerge highlighting the importance to investigate the lesion profile in naturally affected animals. In this report, we review the neuropathology and the neuroinflammation of animal prion diseases in natural hosts from scrapie, going through the zoonotic bovine spongiform encephalopathy (BSE), the chronic wasting disease (CWD) to the newly identified camel prion disease (CPD).

scholarly journals From Prion Diseases to Prion-Like Propagation Mechanisms of Neurodegenerative Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Isabelle Acquatella-Tran Van Ba ◽  
Thibaut Imberdis ◽  
Véronique Perrier
Keyword(s):  
Neurodegenerative Disorders ◽  
Small Rnas ◽  
Prion Diseases ◽  
Cellular Prion Protein ◽  
Spongiform Encephalopathy ◽  
Wasting Disease ◽  
Original Works ◽  
Jakob Disease ◽  
The Brain ◽  
Prion Hypothesis

Prion diseases are fatal neurodegenerative sporadic, inherited, or acquired disorders. In humans, Creutzfeldt-Jakob disease is the most studied prion disease. In animals, the most frequent prion diseases are scrapie in sheep and goat, bovine spongiform encephalopathy in cattle, and the emerging chronic wasting disease in wild and captive deer in North America. The hallmark of prion diseases is the deposition in the brain of PrPSc, an abnormalβ-sheet-rich form of the cellular prion protein (PrPC) (Prusiner 1982). According to the prion hypothesis, PrPSccan trigger the autocatalytic conversion of PrPCinto PrPSc, presumably in the presence of cofactors (lipids and small RNAs) that have been recently identified. In this review, we will come back to the original works that led to the discovery of prions and to the protein-only hypothesis proposed by Dr. Prusiner. We will then describe the recent reports on mammalian synthetic prions and recombinant prions that strongly support the protein-only hypothesis. The new concept of “deformed templating” regarding a new mechanism of PrPScformation and replication will be exposed. The review will end with a chapter on the prion-like propagation of other neurodegenerative disorders, such as Alzheimer’s and Parkinson’s disease and tauopathies.

scholarly journals Microglial Cell Line Established from Prion Protein-Overexpressing Mice Is Susceptible to Various Murine Prion Strains

2006 ◽  
Vol 81 (3) ◽  
pp. 1524-1527 ◽  
Author(s):  
Yoshifumi Iwamaru ◽  
Takato Takenouchi ◽  
Kazumasa Ogihara ◽  
Megumi Hoshino ◽  
Masuhiro Takata ◽  
...  
Keyword(s):  
Cell Line ◽  
Bovine Spongiform Encephalopathy ◽  
Prion Protein ◽  
Cell Lines ◽  
Microglial Cell ◽  
Prion Diseases ◽  
Spongiform Encephalopathy ◽  
Prion Strains ◽  
Microglial Cell Line ◽  
Lines Of Evidence

ABSTRACT Several lines of evidence suggest that microglia have important roles in the pathogenesis of prion diseases. Here, we establish a novel microglial cell line (MG20) from neonatal tga20 mice that overexpress murine prion protein. After exposure to Chandler scrapie, we observed the replication and accumulation of disease-associated forms of the prion protein in MG20 cells up to the 15th passage. Furthermore, MG20 cells were susceptible to ME7, Obihiro scrapie, and bovine spongiform encephalopathy agents. Thus, MG20 cell lines persistently infected with various murine prion strains provide a useful model for the study of the pathogenesis of prion diseases.

scholarly journals Four types of scrapie in goats differentiated from each other and bovine spongiform encephalopathy by biochemical methods

2019 ◽  
Vol 50 (1) ◽  
Author(s):  
Jan P. M. Langeveld ◽  
Laura Pirisinu ◽  
Jorg G. Jacobs ◽  
Maria Mazza ◽  
Isabelle Lantier ◽  
...  
Keyword(s):  
Bovine Spongiform Encephalopathy ◽  
Prion Diseases ◽  
Transmissible Spongiform Encephalopathy ◽  
Small Ruminants ◽  
Infectious Agent ◽  
Spongiform Encephalopathy ◽  
Prion Strain ◽  
Amino Acid Region ◽  
Proteolytic Resistance ◽  
Fatal Consequence

AbstractScrapie in goats has been known since 1942, the archetype of prion diseases in which only prion protein (PrP) in misfolded state (PrPSc) acts as infectious agent with fatal consequence. Emergence of bovine spongiform encephalopathy (BSE) with its zoonotic behaviour and detection in goats enhanced fears that its source was located in small ruminants. However, in goats knowledge on prion strain typing is limited. A European-wide study is presented concerning the biochemical phenotypes of the protease resistant fraction of PrPSc (PrPres) in over thirty brain isolates from transmissible spongiform encephalopathy (TSE) affected goats collected in seven countries. Three different scrapie forms were found: classical scrapie (CS), Nor98/atypical scrapie and one case of CH1641 scrapie. In addition, CS was found in two variants—CS-1 and CS-2 (mainly Italy)—which differed in proteolytic resistance of the PrPresN-terminus. Suitable PrPres markers for discriminating CH1641 from BSE (C-type) appeared to be glycoprofile pattern, presence of two triplets instead of one, and structural (in)stability of its core amino acid region. None of the samples exhibited BSE like features. BSE and these four scrapie types, of which CS-2 is new, can be recognized in goats with combinations of a set of nine biochemical parameters.

scholarly journals Diagnosis of Transmissible Spongiform Encephalopathies in Animals: A Review

2005 ◽  
Vol 17 (6) ◽  
pp. 509-527 ◽  
Author(s):  
Dolores Gavier-Widén ◽  
Michael J. Stack ◽  
Thierry Baron ◽  
Aru Balachandran ◽  
Marion Simmons
Keyword(s):  
Prion Diseases ◽  
Small Ruminants ◽  
Immunohistochemical Analysis ◽  
Considerable Effect ◽  
Proteinase K ◽  
Screening Tests ◽  
Transmissible Spongiform Encephalopathies ◽  
Spongiform Encephalopathy ◽  
Spongiform Encephalopathies ◽  
Prion Strain

Transmissible spongiform encephalopathies (TSEs) in animals include, among others, bovine spongiform encephalopathy (BSE), scrapie, chronic wasting disease, and atypical forms of prion diseases. Diagnosis of TSEs is based on identification of characteristic lesions or on detection of the abnormal prion proteins in tissues, often by use of their partial proteinase K resistance property. Correctly sampling of target tissues is of utmost importance as this has a considerable effect on test sensitivity. Most of the rapid or screening tests are based on ELISA or Western immunoblot (WB) analysis, and many are officially approved. Confirmatory testing is normally performed by use of histologic examination, immunohistochemical analysis, certain WB protocols, or detection of prion fibrils by use of electron microscopy (scrapie-associated fibril). The discriminatory methods for diagnostic use are mostly based on WB technology and provide initial identification of the prion strain, particularly for differentiation of BSE from scrapie in small ruminants. Definitive prion strain characterization is performed by use of bioassays, usually in mice. A burgeoning number of transgenic mice have been developed for TSE studies. Development of new tests with higher sensitivity and of more reliable diagnostic applications for live animals tested for food safety reasons is a rapidly developing field. Ultimately, the choice of a test for TSE diagnosis depends on the rationale for the testing.

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