Preclinical deposition of pathological prion protein PrPSc in muscles of hamsters orally exposed to scrapie

Thomzig, Achim; Schulz‐Schaeffer, Walter; Kratzel, Christine; Mai, Jessica; Beekes, Michael

doi:10.1172/jci21083

Cited by 24 publications

(23 citation statements)

References 37 publications

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“…In support of this possibility we found PrPres detectable by IHC at high levels in white fat associated with skeletal muscle in some tg44 mice ( Figure 4 ). In contrast, other groups did not mention seeing PrPres in muscle-associated fat tissue in animals where myocytes themselves were seen to be positive by IHC [13] – [20] .…”

Section: Discussionmentioning

confidence: 91%

“…It was also noteworthy that in BSE infected cattle, both spleen and skeletal muscle were negative or extremely low by infectivity testing, suggesting that BSE infected cattle differ from other models in this aspect [7] , [8] . PrPres was also detected by western blot in tongue of hamsters and sheep [13] – [15] , skeletal muscles of mice, sheep, and hamsters [12] , [13] , [16] , [17] and cardiac muscle of deer and elk [18] . IHC analysis for PrPres in these tissues was also often positive in myocytes and nerves while fat tissue adjacent to muscle was not noted to be positive [13] – [21] .…”

Section: Introductionmentioning

confidence: 93%

“…Previously, infectivity has been surveyed in multiple organs of sheep [4] , [5] , goats [6] , cattle [7] , [8] , deer [9] , mink [10] , mice [11] , [12] , and hamsters [13] . The highest levels of infectivity and protease-resistant prion protein (PrPres) were found in nervous system tissues such as brain, spinal cord and eye.…”

Section: Introductionmentioning

confidence: 99%

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Detection of Prion Infectivity in Fat Tissues of Scrapie-Infected Mice

Race

Meade-White²,

Oldstone³

et al. 2008

PLoS Pathog

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Distribution of prion infectivity in organs and tissues is important in understanding prion disease pathogenesis and designing strategies to prevent prion infection in animals and humans. Transmission of prion disease from cattle to humans resulted in banning human consumption of ruminant nervous system and certain other tissues. In the present study, we surveyed tissue distribution of prion infectivity in mice with prion disease. We show for the first time detection of infectivity in white and brown fat. Since high amounts of ruminant fat are consumed by humans and also incorporated into animal feed, fat-containing tissues may pose a previously unappreciated hazard for spread of prion infection.

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Section: Discussionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Detection of Prion Infectivity in Fat Tissues of Scrapie-Infected Mice

Race

Meade-White²,

Oldstone³

et al. 2008

PLoS Pathog

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show abstract

“…To accomplish this goal, we monitored prion infection of skeletal muscle in the tongue since prior studies demonstrated that muscle cells of the tongue are susceptible to prion infection (12,22,(31)(32)(33) and since each muscle cell has a single neural synapse, or neuromuscular junction. We demonstrate centrifugal spread of prions from the brain stem to nerve fibers of the tongue, followed by localization to the neuromuscular junction prior to entry into, and replication in, muscle cells.…”

mentioning

confidence: 99%

Axonal and Transynaptic Spread of Prions

Shearin

Bessen

2014

J Virol

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Natural transmission of prion diseases depends upon the spread of prions from the nervous system to excretory or secretory tissues, but the mechanism of prion transport in axons and into peripheral tissue is unresolved. Here, we examined the temporal and spatial movement of prions from the brain stem along cranial nerves into skeletal muscle as a model of axonal transport and transynaptic spread. IMPORTANCEPrion diseases are transmissible and fatal neurodegenerative diseases in which prion dissemination to excretory or secretory tissues is necessary for natural disease transmission. Despite the importance of this pathway, the cellular mechanism of prion transport in axons and into peripheral tissue is unresolved. This study demonstrates anterograde spread of prions within nerve fibers prior to infection of peripheral synapses (i.e., neuromuscular junction) and infection of peripheral tissues (i.e., muscle cells). Within nerve fibers prions were associated with the endosomal-lysosomal pathway prior to entry into muscle cells. Since early prion spread is anterograde and endosome-lysosomal movement within axons is primarily retrograde, these findings suggest that endosome-bound prions may have an alternate fate that directs prions to the peripheral synapse.

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“…Localization of PrP Sc in the muscle spindles of skeletal muscles in the study was consistent with that of atypical BSE in cattle [ 8 ] and natural scrapie in sheep [ 1 ]. In addition, immunolabeled PrP Sc localized at the terminal nerve endings of myofibrils has been reported in hamsters with scrapie and [ 16 ] in rodent and primate models with C-BSE and CJD, respectively [ 6 , 9 , 17 ].…”

mentioning

confidence: 99%

The Presence of Disease-Associated Prion Protein in Skeletal Muscle of Cattle Infected with Classical Bovine Spongiform Encephalopathy

Okada

Miyazawa

Fukuda

et al. 2014

The Journal of Veterinary Medical Science

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The aim of this study was to investigate the presence of disease-associated prion protein (PrPSc) in the skeletal muscle of cattle infected with classical bovine spongiform encephalopathy (C-BSE). The study was carried out systematically in 12 different muscle samples from 43 (3 field and 40 experimental) cases of C-BSE; however, muscle spindles were not available in many of these cases. Therefore, analysis became restricted to a total of 31 muscles in 23 cattle. Even after this restriction, low levels of PrPSc were detected in the muscle spindles of the masseter, intercostal, triceps brachii, psoas major, quadriceps femoris and semitendinosus muscles from 3 field and 6 experimental clinical-stage cases. The present data indicate that small amounts of PrPSc are detectable by immunohistochemistry in the skeletal muscles of animals terminally affected with C-BSE.

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Preclinical deposition of pathological prion protein PrPSc in muscles of hamsters orally exposed to scrapie

Cited by 24 publications

References 37 publications

Detection of Prion Infectivity in Fat Tissues of Scrapie-Infected Mice

Detection of Prion Infectivity in Fat Tissues of Scrapie-Infected Mice

Axonal and Transynaptic Spread of Prions

The Presence of Disease-Associated Prion Protein in Skeletal Muscle of Cattle Infected with Classical Bovine Spongiform Encephalopathy

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