Accumulation of Pathogenic Prion Protein (PrPSc) in Nervous and Lymphoid Tissues of Sheep with Subclinical Scrapie

All sheep older than 1 year of age from a flock of the Rygja breed in which clinical scrapie was detected for the first time in two animals (4%) were examined for accumulation of pathogenic prion protein (PrPSc) by immunohistochemistry in the obex, the cerebellum, and the medial retrophayngeal lymph node. In addition, six lambs, 2–3 months old, all offspring of PrPSc-positive dams, were examined for PrPSc in the ileal Peyers' patch (IPP), the distal jejunal lymph node, the spleen, and the medial retropharyngeal lymph node (RPLN). In this flock, 35% (17/48) of the adult sheep showed accumulation of PrPSc, an eightfold increase compared with clinical disease. All positives carried susceptible PrP genotypes. Three sheep had deposits of PrPSc in the RPLN and not in the brain, suggesting that this organ, easily accessible at slaughter, is suitable for screening purposes. Two 7-year-old clinically healthy homozygous V136Q171 ewes showed sparse immunostaining in the central nervous system and may have been infected as adults. Further, two littermates, 86-days-old, showed PrPSc in the IPP. Interestingly, one of these lambs had the intermediate susceptible PrP genotype, VA136QR171. In addition to early immunolabeling in the dorsal motor nucleus of the vagal nerve, a few of the sheep had early involvement of the cerebellum. In fact, a 2-year-old sheep had sparse deposits of PrPSc in the cerebellum only. Because experimental bovine spongiform encephalopathy (BSE) in sheep seems to behave in a similar manner as natural scrapie, these results, particularly regarding spread of infectivity, may have implications for the handling of BSE should it be diagnosed in sheep.

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Molecular Detection of Cellular Prion Protein in Brain Tissues of Black Bengal Goats in Bangladesh

Journal of Tropical Resources and Sustainable Science (JTRSS) ◽

10.47253/jtrss.v3i2.519 ◽

2015 ◽

Vol 3 (2) ◽

pp. 1-4

Author(s):

Nasrin Sultana ◽

Mohd Zahirul Islam Khan ◽

Emdadul Haque Choudhury ◽

Md Rafiqul Islam

Keyword(s):

Prion Protein ◽

Molecular Detection ◽

Cellular Prion Protein ◽

The Central Nervous System ◽

Membrane Bound ◽

Polymerase Chain ◽

First Time ◽

The Brain ◽

Prp Gene ◽

Brain Tissues

The cellular prion protein (PrPC) is a membrane-bound glycoprotein mainlypresent in the central nervous system which is necessary for the establishmentand further evolution of prion disease in human and animals. The aim of thepresent study was to investigate the PrPC protein in brain tissues of black Bengalgoat. Fifteen brain tissues were collected from different slaughter houses ofthree districts (Mymensingh, Manikgonj and Netrokona) of Bangladesh duringJanuary to February, 2011. The PrPC protein was detected in the brain tissuesof black Bengal goats using polymerase chain reaction. The result showed allpositive (100%) of the amplified samples. The standardized PCR could be usedfor detection of PrPC protein in different tissues of animals and humans.Sequencing of PrP gene in the black Bengal goats for the risk assessment ofscrapie is needed for further study. To our knowledge, detection of PrPC proteinin the brain tissues of indigenous goats is the first time in Bangladesh.

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Abnormal prion protein in genetically resistant sheep from a scrapie-infected flock

Journal of General Virology ◽

10.1099/vir.0.80220-0 ◽

2004 ◽

Vol 85 (11) ◽

pp. 3483-3486 ◽

Cited By ~ 25

Author(s):

J.-Y. Madec ◽

S. Simon ◽

S. Lezmi ◽

A. Bencsik ◽

J. Grassi ◽

...

Keyword(s):

Prion Protein ◽

Sandwich Elisa ◽

Protein A ◽

Cellular Prion Protein ◽

Transmissible Spongiform Encephalopathies ◽

Motor Nucleus ◽

Entry Site ◽

Spongiform Encephalopathies ◽

Dorsal Motor Nucleus ◽

The Brain

The central molecular event in transmissible spongiform encephalopathies, such as scrapie in sheep, is the accumulation in tissues of an abnormal isoform of the cellular prion protein. A previous investigation of 26 sheep showed that the accumulation of PrPres in brain correlated more with the prnp genotype than with the severity of the clinical disease. Here, the ability of a sandwich ELISA to detect PrPres distribution in the brain was demonstrated. Immunohistochemistry also strongly supported the hypothesis that the dorsal motor nucleus of the vagus nerve is the possible entry site in the brain for the scrapie agent. Remarkably, three asymptomatic (or possibly asymptomatic for scrapie) sheep carrying an allele known to be associated with clinical scrapie resistance (ARR), which were negative for the detection of PrPres by Western blotting and immunohistochemistry, were positive for the presence of PrPres by ELISA, raising the possibility of carriers resistant to the disease and possibly contributing to the persistence of scrapie in certain flocks.

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Early accumulation of PrPSc in gut-associated lymphoid and nervous tissues of susceptible sheep from a Romanov flock with natural scrapie

Journal of General Virology ◽

10.1099/0022-1317-81-12-3115 ◽

2000 ◽

Vol 81 (12) ◽

pp. 3115-3126 ◽

Cited By ~ 292

Author(s):

Olivier Andréoletti ◽

Patricia Berthon ◽

Daniel Marc ◽

Pierre Sarradin ◽

Jeanne Grosclaude ◽

...

Keyword(s):

Lymph Node ◽

Mediastinal Lymph Node ◽

Oral Route ◽

Cellular Level ◽

Lymphoid Tissues ◽

Entry Site ◽

The Central Nervous System ◽

Natural Scrapie ◽

Scrapie Infection ◽

Secondary Lymphoid Organs

The immune system is known to be involved in the early phase of scrapie pathogenesis. However, the infection route of naturally occurring scrapie and its spread within the host are not entirely known. In this study, the pathogenesis of scrapie was investigated in sheep of three PrP genotypes, from 2 to 9 months of age, which were born and raised together in a naturally scrapie-affected Romanov flock. The kinetics of PrPSc accumulation in sheep organs were determined by immunohistochemistry. PrPSc was detected only in susceptible VRQ/VRQ sheep, from 2 months of age, with an apparent entry site at the ileal Peyer’s patch as well as its draining mesenteric lymph node. At the cellular level, PrPSc deposits were associated with CD68-positive cells of the dome area and B follicles before being detected in follicular dendritic cells. In 3- to 6-month-old sheep, PrPSc was detected in most of the gut-associated lymphoid tissues (GALT) and to a lesser extent in more systemic lymphoid formations such as the spleen or the mediastinal lymph node. All secondary lymphoid organs showed a similar intensity of PrPSc-immunolabelling at 9 months of age. At this time-point, PrPSc was also detected in the autonomic myenteric nervous plexus and in the nucleus parasympathicus nervi X of the brain stem. These data suggest that natural scrapie infection occurs by the oral route via infection of the Peyer’s patches followed by replication in the GALT. It may then spread to the central nervous system through the autonomic nervous fibres innervating the digestive tract.

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Distribution of Protease-resistant Prion Protein and Spongiform Encephalopathy in Free-ranging Mule Deer (Odocoileus hemionus) with Chronic Wasting Disease

Veterinary Pathology ◽

10.1354/vp.39-5-546 ◽

2002 ◽

Vol 39 (5) ◽

pp. 546-556 ◽

Cited By ~ 51

Author(s):

T. R. Spraker ◽

R. R. Zink ◽

B. A. Cummings ◽

C. J. Sigurdson ◽

M. W. Miller ◽

...

Keyword(s):

Prion Protein ◽

Chronic Wasting Disease ◽

Mule Deer ◽

Odocoileus Hemionus ◽

Palatine Tonsil ◽

Spongiform Encephalopathy ◽

Motor Nucleus ◽

Serial Sections ◽

Wasting Disease ◽

The Brain

Serial sections of brain and palatine tonsil were examined by immunohistochemical staining (IHC) using monoclonal antibody F89/160.1.5 for detecting protease-resistant prion protein (PrPres) in 35 hunterkilled mule deer ( Odocoileus hemionus) with chronic wasting disease. Serial sections of brain were stained with hematoxylin and eosin and examined for spongiform encephalopathy (SE). Clinical signs of disease were not observed in any of these deer. On the basis of the location and abundance of IHC and the location and severity of SE, deer were placed into four categories. Category 1 ( n = 8) was characterized by IHC in the palatine tonsil with no evidence of IHC or SE in the brain. Category 2 ( n = 13) was characterized by IHC in the palatine tonsil and IHC with or without SE in the dorsal motor nucleus of the vagus nerve (DMNV). Category 3 ( n = 2) was characterized by IHC in the palatine tonsil, IHC with SE in the myelencephalon, and IHC without SE in the hypothalamus. Category 4 ( n = 12) was characterized by IHC in the palatine tonsil and IHC with SE throughout the brain. Category 1 may represent early lymphoid tissue localization of PrPres. The DMNV appears to be the most consistent single neuroanatomic site of detectable PrPres. Categories 2–4 may represent a progression of spread of PrPres and SE throughout the brain. IHC in tonsil and brain and SE in brain were not detected in 208 control deer.

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Baroreflex control of heart rate by oxytocin in the solitary-vagal complex

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00806.2000 ◽

2002 ◽

Vol 282 (2) ◽

pp. R537-R545 ◽

Cited By ~ 87

Author(s):

Keila T. Higa ◽

Eliana Mori ◽

Fabiano F. Viana ◽

Mariana Morris ◽

Lisete C. Michelini

Keyword(s):

Heart Rate ◽

Male Rats ◽

Motor Nucleus ◽

Baroreflex Control ◽

Dorsal Motor Nucleus ◽

Loading And Unloading ◽

Reflex Control ◽

Exercise Induced ◽

Baroreceptor Reflex Control ◽

The Brain

Previous work demonstrated that oxytocinergic projections to the solitary vagal complex are involved in the restraint of exercise-induced tachycardia (2). In the present study, we tested the idea that oxytocin (OT) terminals in the solitary vagal complex [nucleus of the solitary tract (NTS)/dorsal motor nucleus of the vagus (DMV)] are involved in baroreceptor reflex control of heart rate (HR). Studies were conducted in male rats instrumented for chronic cardiovascular monitoring with a cannula in the NTS/DMV for brain injections. Basal mean arterial pressure and HR and reflex HR responses during loading and unloading of the baroreceptors (phenylephrine/sodium nitroprusside intravenously) were recorded after administration of a selective OT antagonist (OTant) or OT into the NTS/DMV. The NTS/DMV was selected for study because this region contains such a specific and dense concentration of OT-immunoreactive terminals. Vehicle injections served as a control. OT and OTant changed baroreflex control of HR in opposite directions. OT (20 pmol) increased the maximal bradycardic response (from −56 ± 9 to −75 ± 11 beats/min), whereas receptor blockade decreased the bradycardia (from −61 ± 13 to −35 ± 2 beats/min). OTant also reduced the operating range of the reflex, thus decreasing baroreflex gain (from −5.68 ± 1.62 to −2.83 ± 1.05 beats · min−1 · mmHg−1). OT injected into the NTS/DMV of atenolol-treated rats still potentiated the bradycardic responses to pressor challenges, whereas OT injections had no effect in atropine-treated rats. The brain stem effect was specific because neither vehicle administration nor injection of OT or OTant into the fourth cerebral ventricle had any effect. Our data suggest that OT terminals in the solitary vagal complex modulate reflex control of the heart, acting to facilitate vagal outflow and the slowdown of the heart.

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Sporadic Creutzfeldt-Jakob Disease: Prion Pathology in Medulla Oblongata—Possible Routes of Infection and Host Susceptibility

BioMed Research International ◽

10.1155/2015/396791 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Diego Iacono ◽

Sergio Ferrari ◽

Matteo Gelati ◽

Gianluigi Zanusso ◽

Sara Mariotto ◽

...

Keyword(s):

Prion Protein ◽

Environmental Exposure ◽

Phenotypic Variability ◽

Host Susceptibility ◽

Motor Nucleus ◽

Host Genotype ◽

Dorsal Motor Nucleus ◽

Jakob Disease ◽

Medullary Nuclei ◽

Codon 129

Sporadic Creutzfeldt-Jakob disease (sCJD), the most frequent human prion disorder, is characterized by remarkable phenotypic variability, which is influenced by the conformation of the pathologic prion protein and the methionine/valine polymorphic codon 129 of the prion protein gene. While the etiology of sCJD remains unknown, it has been hypothesized that environmental exposure to prions might occur through conjunctival/mucosal contact, oral ingestion, inhalation, or simultaneous involvement of the olfactory and enteric systems. We studied 21 subjects with definite sCJD to assess neuropathological involvement of the dorsal motor nucleus of the vagus and other medullary nuclei and to evaluate possible associations with codon 129 genotype and prion protein conformation. The present data show that prion protein deposition was detected in medullary nuclei of distinct sCJD subtypes, either valine homozygous or heterozygous at codon 129. These findings suggest that an “environmental exposure” might occur, supporting the hypothesis that external sources of contamination could contribute to sCJD in susceptible hosts. Furthermore, these novel data could shed the light on possible causes of sCJD through a “triple match” hypothesis that identify environmental exposure, host genotype, and direct exposure of specific anatomical regions as possible pathogenetic factors.

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Prion Diseases and the Gastrointestinal Tract

Canadian Journal of Gastroenterology ◽

10.1155/2006/184528 ◽

2006 ◽

Vol 20 (1) ◽

pp. 18-24 ◽

Cited By ~ 21

Author(s):

Gwynivere A Davies ◽

Adam R Bryant ◽

John D Reynolds ◽

Frank R Jirik ◽

Keith A Sharkey

Keyword(s):

Nervous System ◽

Dendritic Cells ◽

Enteric Nervous System ◽

Prion Protein ◽

Cellular Prion Protein ◽

Transmissible Spongiform Encephalopathies ◽

Spongiform Encephalopathy ◽

Gi Tract ◽

Spongiform Encephalopathies ◽

The Brain

The gastrointestinal (GI) tract plays a central role in the pathogenesis of transmissible spongiform encephalopathies. These are human and animal diseases that include bovine spongiform encephalopathy, scrapie and Creutzfeldt-Jakob disease. They are uniformly fatal neurological diseases, which are characterized by ataxia and vacuolation in the central nervous system. Alhough they are known to be caused by the conversion of normal cellular prion protein to its infectious conformational isoform (PrPsc) the process by which this isoform is propagated and transported to the brain remains poorly understood. M cells, dendritic cells and possibly enteroendocrine cells are important in the movement of infectious prions across the GI epithelium. From there, PrPscpropagation requires B lymphocytes, dendritic cells and follicular dendritic cells of Peyer’s patches. The early accumulation of the disease-causing agent in the plexuses of the enteric nervous system supports the contention that the autonomic nervous system is important in disease transmission. This is further supported by the presence of PrPscin the ganglia of the parasympathetic and sympathetic nerves that innervate the GI tract. Additionally, the lymphoreticular system has been implicated as the route of transmission from the gut to the brain. Although normal cellular prion protein is found in the enteric nervous system, its role has not been characterized. Further research is required to understand how the cellular components of the gut wall interact to propagate and transmit infectious prions to develop potential therapies that may prevent the progression of transmissible spongiform encephalopathies.

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Immunohistochemical Detection and Distribution of Prion Protein in a Goat with Natural Scrapie

Journal of Veterinary Diagnostic Investigation ◽

10.1177/104063870301500210 ◽

2003 ◽

Vol 15 (2) ◽

pp. 157-162 ◽

Cited By ~ 25

Author(s):

Reginald A. Valdez ◽

Matthew J. Rock ◽

Anne K. Anderson ◽

Katherine I. O'Rourke

Keyword(s):

Prion Protein ◽

Precise Determination ◽

Lymphoid Tissues ◽

Large Sample Size ◽

Parasympathetic Ganglia ◽

Peripheral Lymph ◽

Formalin Fixed Paraffin ◽

Formalin Fixed Paraffin Embedded ◽

Natural Scrapie ◽

Diagnostic Sensitivity And Specificity

Formalin-fixed, paraffin-embedded tissue sections from a 3-year-old female Angora goat suffering from clinical scrapie were immunostained after hydrated autoclaving using a monoclonal antibody (mAb, F99/97.6.1; IgG1) specific for a conserved epitope on the prion protein. Widespread and prominent deposition of the scrapie isoform of the prion protein (PrPSc) was observed in the brain, brainstem, spinal cord, retina, postganglionic neurons associated with parasympathetic ganglia of myenteric and submucosal plexuses, Peyer's patches, peripheral lymph nodes, and pharyngeal and palatine tonsils. The goat was homozygous for PrP alleles encoding 5 octapeptide repeat sequences in the N-terminal region of the prion protein and isoleucine at codon 142, a genotype associated with high susceptibility and short incubation times in goats. The results of this study indicate that mAb F99/97.6.1 is useful for detection of PrPSc deposition, and this is a specific and reliable immunohistochemical adjunct to histopathology for diagnosis of natural caprine scrapie, although precise determination of the diagnostic sensitivity and specificity of the assay as a diagnostic test for scrapie in goats will require examination of a sufficiently large sample size. As with ovine scrapie, prion protein is widely distributed in the central and peripheral nervous systems, gastrointestinal tract, and lymphoid tissues in natural caprine scrapie.

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EPIDEMIOLOGY AND SURVIVAL OF PATIENTS WITH MALIGNANT TUMORS OF THE BRAIN (C71). POPULATION-BASED STUDY

Problems in oncology ◽

10.37469/0507-3758-2020-66-5-489-499 ◽

2020 ◽

Vol 66 (5) ◽

pp. 489-499

Author(s):

Vakhtang Merabishvili ◽

Kalyango Kennet ◽

M. Valkov ◽

Andrey Dyachenko

Keyword(s):

Malignant Tumors ◽

Cranial Nerves ◽

Cancer Registries ◽

Population Based ◽

Malignant Neoplasms ◽

Incidence And Mortality ◽

Icd 10 ◽

The Central Nervous System ◽

First Time ◽

The Brain

Malignant neoplasms of the brain (BMN) in accordance with the international classification of the diseases (ICD-10) belong to the rubric C71. However, in the world and Russia it is customary to understand this term as the entire block of localizations related to the brain - rubrics C70-71. The topographic codes C70 (meninges), C71 (brain) and C72 (spinal cord, cranial nerves and other parts of the central nervous system) make up a small proportion among MN in general. In addition, all the summary data WHO-IARC and Russia as a rule aggregate the CNS tumors under the three heading ICD - 10 (ICDO-3) C70-72. With the developments in Russia of the system of Population cancer registries, it became possible to study the patterns of dynamics of incidence and to calculate the survival rate of patients with malignant necrosis in each ICD-10 section. This study presents the population-based analysis of incidence and mortality from BMN using available sources and, for the first time in Russia, the analysis of the dynamics of the survival among the patients with BMN under the rubric C71 is performed.

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