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

Andréoletti, Olivier; Berthon, Patricia; Marc, Daniel; Sarradin, Pierre; Grosclaude, Jeanne; Keulen, Lucien van; Schelcher, F.; Elsen, Jean-Michel; Lantier, Frédéric

doi:10.1099/0022-1317-81-12-3115

Cited by 383 publications

(398 citation statements)

References 51 publications

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“…In natural and experimental diseases, the Wrst neural tissues in which PrP Sc can be highlighted both in sheep and mice scrapie, cattle bovine spongiform encephalopathy (BSE) and deer chronic wasting disease (CWD) is the enteric nervous system (ENS) of the gut (Andreoletti et al 2000;van Keulen et al 2000;Sigurdson et al 2001;Iwata et al 2006). This intramural nervous system is composed of two networks, the submucosal and the myenteric plexi, which contain the neuronal cell bodies and their processes.…”

Section: Introductionmentioning

confidence: 99%

Spreading of prions from the immune to the peripheral nervous system: a potential implication of dendritic cells

Dorban

Defaweux

Heinen

et al. 2010

Histochem Cell Biol

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The implication of dendritic cells (DCs) in the peripheral spreading of prions has increased in the last few years. It has been recently described that DCs can transmit prions to primary neurons from the central nervous system. In order to improve the understanding of the earliest steps of prion peripheral neuroinvasion, we studied, using an in vitro model, the eVect of exposing primary peripheral neurons to scrapie-infected lymphoid cells. Thanks to this system, there is evidence that bone marrow dendritic cells (BMDCs) are in connection with neurites of peripheral neurons via cytoplasmic extensions. BMDCs are competent to internalize prions independently from the expression of cellular prion protein (PrP C ) and have the capacity to transmit detergent-insoluble, relatively proteinase K-resistant prion protein (PrP Sc ) to peripheral neurons after 96 h of coculture. Furthermore, we conWrmed the special status of the peripheral nervous system in front of prion diseases.Contrary to central neurons, PrP Sc infection does not disturb survival and neurite outgrowth. Our model demonstrates that PrP Sc -loaded dendritic cells and peripheral nerve Wbers that are included in neuroimmune interfaces can initiate and spread prion neuroinvasion.

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Section: Introductionmentioning

confidence: 99%

Spreading of prions from the immune to the peripheral nervous system: a potential implication of dendritic cells

Dorban

Defaweux

Heinen

et al. 2010

Histochem Cell Biol

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show abstract

“…Except in mice, prionin proteins are comprised of four or five equally spaced β-sheets and it has been proposed that these interact with PrP C and participate in their conversion to PrP Sc 3 . It is also reported that expression of prionins in subjects results in the expression of specific anti-prionin endogenous antibodies and Altegen Inc. have exploited this to develop a blood-based TSE ELISA test to detect anti-prionin antibodies 3,4 . It is claimed that the Altegen test is able to detect endogenous anti-bovine, anti-scrapie and anti-CJD prionin antibodies in as little as 1-2 µL serum and results are obtained within 3 h. The test reportedly indicates TSE infection 2-3 years post infection and is highly sensitive and specific in all premortem subjects.…”

Section: Prioninmentioning

confidence: 99%

“…The spread of PrP Sc to the lymphoid organs is thought to be mediated by the lymphoreticular system. Studies have shown that the eventual transport of PrP Sc to the CNS is mediated by axonal transport within the parasympathetic and the sympathetic nervous system [4,62,63,109,115,116].…”

Section: Introductionmentioning

confidence: 99%

The use of non-prion biomarkers for the diagnosis of Transmissible Spongiform Encephalopathies in the live animal

Parveen

Moorby²,

Allison³

et al. 2005

Vet. Res.

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-Scrapie and bovine spongiform encephalopathy (BSE) are major global concerns and the emergence of variant Creutzfeldt-Jakob disease (vCJD) has caused turmoil for blood transfusion services and hospitals worldwide. Recent reports of iatrogenic CJD (iCJD) cases following blood transfusions from Transmissible Spongiform Encephalopathies (TSE)-infected donors have fuelled this concern. Major diagnostic tests for BSE and scrapie are conducted post-mortem from animals in late stages of the disease. Although the lymphoreticular system is involved in the earlier pathogenesis of some forms of sheep scrapie and vCJD, which presents great opportunity for diagnostic development, other TSE diseases (some strains of scrapie, sporadic CJD (sCJD) and bovine BSE) do not present such a diagnostic opportunity. Thus, there is an urgent need for premortem tests that differentiate between healthy and diseased individuals at early stages of illness, in accessible samples such as blood and urine using less invasive procedures. This review reports on the current state of progress in the development and use of prion and non-prion biomarkers in the diagnosis of TSE diseases. Some of these efforts have concentrated on improving the sensitivity of PrP Sc detection to allow in vivo diagnosis at low abundances of PrP Sc whilst others have sought to identify non-prion protein biomarkers of TSE disease, many of which are still at early stages of development. In this review we comment upon the limitations of prion based tests and review current research on the development of tests for TSE that rely on non-prion disease markers in body fluids that may allow preclinical disease diagnosis.

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“…The sequential detection of abnormal prion protein in lymphoreticular tissue and along neural projections to the CNS after peripheral infection in various animal models led to the conclusion that these tissues are involved in the spread of the TSE agent to the CNS [3,7,17,28,35,44,46]. The sciatic nerve is a useful structure for monitoring the centripetal neural spread of the scrapie agent [29] and rapid disease onset was observed after intrasciatic injections of strains of transmissible mink encephalopathy (TME) in rodents [4].…”

Section: Introductionmentioning

confidence: 99%

Propagation of scrapie in peripheral nerves after footpad infection in normal and neurotoxin exposed hamsters

et al. 2007

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-As is known from various animal models, the spread of agents causing transmissible spongiform encephalopathies (TSE) after peripheral infection affects peripheral nerves before reaching the central nervous system (CNS) and leading to a fatal end of the disease. The lack of therapeutic approaches for TSE is partially due to the limited amount of information available on the involvement of host biological compartments and processes in the propagation of the infectious agent. The in vivo model presented here can provide information on the spread of the scrapie agent via the peripheral nerves of hamsters under normal and altered axonal conditions. Syrian hamsters were unilaterally footpad (f.p.) infected with scrapie. The results of the spatiotemporal ultrasensitive immunoblot-detection of scrapie-associated prion protein (PrP Sc ) in serial nerve segments of both distal sciatic nerves could be interpreted as a centripetal and subsequent centrifugal neural spread of PrP Sc for this route of infection. In order to determine whether this propagation is dependent on main components in the axonal cytoskeleton (e.g. neurofilaments, also relevant for the component 'a' of slow axonal transport mechanisms), hamsters were treated -in an additional experiment-with the neurotoxin ß,ß'-iminodiproprionitrile (IDPN) around the beginning of the scrapie infection. A comparison of the Western blot signals of PrP Sc in the ipsilateral and in the subsequently affected contralateral sciatic nerve segments with the results revealed from IDPN-untreated animals at preclinical and clinical stages of the TSE disease, indicated similar amounts of PrP Sc . Furthermore, the mean survival time was unchanged in both groups. This in vivo model, therefore, suggests that the propagation of PrP Sc along peripheral nerves is not dependent on an intact neurofilament component of the axonal cytoskeleton. Additionally, the model indicates that the spread of PrP Sc is not mediated by the slow component 'a' of the axonal transport mechanism.scrapie / PrP Sc / nerve / footpad / IDPN

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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

Cited by 383 publications

References 51 publications

Spreading of prions from the immune to the peripheral nervous system: a potential implication of dendritic cells

Spreading of prions from the immune to the peripheral nervous system: a potential implication of dendritic cells

The use of non-prion biomarkers for the diagnosis of Transmissible Spongiform Encephalopathies in the live animal

Propagation of scrapie in peripheral nerves after footpad infection in normal and neurotoxin exposed hamsters

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