Accumulation of Pathogenic Prion Protein (PrP<sup>Sc</sup>) in Nervous and Lymphoid Tissues of Sheep with Subclinical Scrapie

Ersdal, Cecilie; Ulvund, Martha J.; Benestad, Sylvie L.; Tranulis, Michael A.

doi:10.1354/vp.40-2-164

Cited by 61 publications

(47 citation statements)

References 49 publications

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“…Prion infection of taste buds has not been previously described, but a loss of taste and smell was reported to be a presenting symptom in a case of variant CreutzfeldtJakob disease, suggesting involvement of the gustatory and olfactory systems in prion-induced neurodegeneration (44). In the brain stem, the rostral portion of the nucleus of the solitary tract (NST) is involved in gustatory function; this nucleus is a target for prion infection in scrapie in sheep (17,31,45), CWD in deer (48), and bovine spongiform encephalopathy in cattle (56,57). Based on our findings that HY TME agent infection in the brain stem can spread to taste buds via sensory nerves that synapse in this nucleus, it will be necessary to investigate whether the prion agent can also spread to the taste buds in ruminants.…”

Section: Discussionmentioning

confidence: 99%

Prion Infection of Oral and Nasal Mucosa

DeJoia

Moreaux

O'Connell

et al. 2006

J Virol

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Centrifugal spread of the prion agent to peripheral tissues is postulated to occur by axonal transport along nerve fibers. This study investigated the distribution of the pathological isoform of the protein (PrP Sc ) in the tongues and nasal cavities of hamsters following intracerebral inoculation of the HY strain of the transmissible mink encephalopathy (TME) agent. We report that PrP Sc deposition was found in the lamina propria, taste buds, and stratified squamous epithelium of fungiform papillae in the tongue, as well as in skeletal muscle cells. Using laser scanning confocal microscopy, PrP Sc was localized to nerve fibers in each of these structures in the tongue, neuroepithelial taste cells of the taste bud, and, possibly, epithelial cells. This PrP Sc distribution was consistent with a spread of HY TME agent along both somatosensory and gustatory cranial nerves to the tongue and suggests subsequent synaptic spread to taste cells and epithelial cells via peripheral synapses. In the nasal cavity, PrP Sc accumulation was found in the olfactory and vomeronasal epithelium, where its location was consistent with a distribution in cell bodies and apical dendrites of the sensory neurons. Prion spread to these sites is consistent with transport via the olfactory nerve fibers that descend from the olfactory bulb. Our data suggest that epithelial cells, neuroepithelial taste cells, or olfactory sensory neurons at chemosensory mucosal surfaces, which undergo normal turnover, infected with the prion agent could be shed and play a role in the horizontal transmission of animal prion diseases.

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Section: Discussionmentioning

confidence: 99%

Prion Infection of Oral and Nasal Mucosa

DeJoia

Moreaux

O'Connell

et al. 2006

J Virol

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“…The specific pathways may include parasympathetic nerve fibers of postganglionic origin that emanate from intrapancreatic ganglia , Brunicardi et al 1995, which are controlled by preganglionic fibers originating almost exclusively in the dorsal motor nucleus of the vagus (DMNV; , Berthoud & Powley 1990, Brunicardi et al 1995. Interestingly, the DMNV is an early target of PrP Sc infection in hamsters receiving oral inoculation with the 139H scrapie agent (Beekes et al 1998), as well as in deer with naturally occurring chronic wasting disease (Sigurdson et al 2001) and in sheep with clinical scrapie (van Keulen et al 2000, Ersdal et al 2003. Several studies show that parasympathetic neurotransmitters are localized to islet parasympathetic nerves, are released directly by vagal stimulation and can induce insulin secretion .…”

Section: Prpmentioning

confidence: 99%

Prominent pancreatic endocrinopathy and altered control of food intake disrupt energy homeostasis in prion diseases

Bailey

Berardinelli

Rocke

et al. 2008

Journal of Endocrinology

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Prion diseases are fatal neurodegenerative diseases that can induce endocrinopathies. The basis of altered endocrine function in prion diseases is not well understood, and the purpose of this study was to investigate the spatiotemporal relationship between energy homeostasis and prion infection in hamsters inoculated with either the 139H strain of scrapie agent, which induces preclinical weight gain, or the HY strain of transmissible mink encephalopathy (TME), which induces clinical weight loss. Temporal changes in body weight, feed, and water intake were measured as well as both non-fasted and fasted concentrations of serum glucose, insulin, glucagon, b-ketones, and leptin. In 139H scrapie-infected hamsters, polydipsia, hyperphagia, non-fasted hyperinsulinemia with hyperglycemia, and fasted hyperleptinemia were found at preclinical stages and are consistent with an anabolic syndrome that has similarities to type II diabetes mellitus and/or metabolic syndrome X. In HY TME-infected hamsters, hypodipsia, hypersecretion of glucagon (in both non-fasted and fasted states), increased fasted b-ketones, fasted hypoglycemia, and suppressed non-fasted leptin concentrations were found while feed intake was normal. These findings suggest a severe catabolic syndrome in HY TME infection mediated by chronic increases in glucagon secretion. In both models, alterations of pancreatic endocrine function were not associated with PrP Sc deposition in the pancreas. The results indicate that prominent endocrinopathy underlies alterations in body weight, pancreatic endocrine function, and intake of food. The prion-induced alterations of energy homeostasis in 139H scrapie-or HY TME-infected hamsters could occur within areas of the hypothalamus that control food satiety and/or within autonomic centers that provide neural outflow to the pancreas.

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“…Sc has been found in the hypoglossal nucleus (9,37,43), the nucleus of the solitary tract (9,34,37,43), and several of the trigeminal nuclei (9,34,37,43,44). The ability of the prion agent to establish infection in brain nuclei that contribute to, or synapse with, the four cranial nerves that innervate the tongue suggests that this could be a pathway for centrifugal prion agent spread.…”

Section: Fig 4 Confocal Microscopy Of Prpmentioning

confidence: 99%

Prion Infection of Skeletal Muscle Cells and Papillae in the Tongue

Mulcahy¹,

Bartz²,

Kincaid

et al. 2004

J Virol

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The presence of the prion agent in skeletal muscle is thought to be due to the infection of nerve fibers located within the muscle. We report here that the pathological isoform of the prion protein, PrP Sc , accumulates within skeletal muscle cells, in addition to axons, in the tongue of hamsters following intralingual and intracerebral inoculation of the HY strain of the transmissible mink encephalopathy agent. Localization of PrP Sc to the neuromuscular junction suggests that this synapse is a site for prion agent spread between motor axon terminals and muscle cells. Following intracerebral inoculation, the majority of PrP Sc in the tongue was found in the lamina propria, where it was associated with sensory nerve fibers in the core of the lingual papillae. PrP Sc staining was also identified in the stratified squamous epithelium of the lingual mucosa. These findings indicate that prion infection of skeletal muscle cells and the epithelial layer in the tongue can be established following the spread of the prion agent from nerve terminals and/or axons that innervate the tongue. Our data suggest that ingestion of meat products containing prion-infected tongue could result in human exposure to the prion agent, while sloughing of prion-infected epithelial cells at the mucosal surface of the tongue could be a mechanism for prion agent shedding and subsequent prion transmission in animals.

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

Cited by 61 publications

References 49 publications

Prion Infection of Oral and Nasal Mucosa

Prion Infection of Oral and Nasal Mucosa

Prominent pancreatic endocrinopathy and altered control of food intake disrupt energy homeostasis in prion diseases

Prion Infection of Skeletal Muscle Cells and Papillae in the Tongue

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

Cited by 61 publications

References 49 publications

Prion Infection of Oral and Nasal Mucosa

Prion Infection of Oral and Nasal Mucosa

Prominent pancreatic endocrinopathy and altered control of food intake disrupt energy homeostasis in prion diseases

Prion Infection of Skeletal Muscle Cells and Papillae in the Tongue

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