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/jci200421083

Cited by 55 publications

(70 citation statements)

References 35 publications

(39 reference statements)

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“…The late centrifugal spread of PrP TSE from the CNS to muscle in orally BSE-infected mice is also consistent with observations in other experimental models (Thomzig et al, 2004;Herzog et al, 2005) or in scrapie-infected sheep (Andréoletti et al, 2004), where the CNS plays a primary role in the dissemination of infectivity to muscles (Beekes & McBride, 2007).…”

supporting

confidence: 88%

“…The presence and distribution of infectivity or PrP TSE accumulation in muscles of 'natural' TSE infections differ in different host-strain combinations (Andréoletti et al, 2004;Angers et al, 2006;Beekes & McBride, 2007;Bosque et al, 2002;Casalone et al, 2005;Glatzel et al, 2003;Herzog et al, 2005;Peden et al, 2006;Thomzig et al, 2004Thomzig et al, , 2006. This heterogeneity has also been observed in experimental models of TSEs.…”

mentioning

confidence: 94%

“…This result is similar to what has been found in sheep infected orally with scrapie, where muscle PrP TSE was detected during the first one-quarter of the incubation period (Andréoletti et al, 2004). Interestingly, this phenomenon does not occur in all TSE models; for example, in hamsters fed with 263K scrapie, muscles only became PrP TSE -positive near clinical onset (Thomzig et al, 2004).…”

mentioning

confidence: 98%

“…This heterogeneity has also been observed in experimental models of TSEs. In hamsters fed with 263K scrapie, PrP TSE and infectivity accumulate in muscles much later than in the CNS, suggesting a centrifugal neural spread of infection from the CNS into muscles (Thomzig et al, 2004 neuromuscular junctions and muscle spindles in scrapieor TME-infected hamsters (Mulcahy et al, 2004;Thomzig et al, 2004) and in scrapie-infected sheep (Andréoletti et al, 2004). In mice experimentally infected intracerebrally with BSE, the presence of PrP TSE in muscles is more restricted than in hamsters (Thomzig et al, 2003(Thomzig et al, , 2006, but it is similar to that found in CJD patients (Glatzel et al, 2003;Peden et al, 2006) and in sheep with scrapie (Andréoletti et al, 2004).…”

mentioning

confidence: 99%

“…Control animals (n59) were fed pellets soaked with normal mouse-brain homogenate and were sacrificed following the schedule described for BSE-infected mice. All animals were autopsied and brain, spleen and a set of nine different muscles were sampled and either fixed in formalin for histological examination or frozen at 270 u C for PrP27-30 (the protease-resistant form of PrP TSE ) purification, biochemical and paraffin-embedded tissue (PET)-blot analyses (Thomzig et al, 2003(Thomzig et al, , 2004(Thomzig et al, , 2006. All mice allowed to survive became symptomatic, with a mean±SD incubation period of 368.3±13.7 days (n510), confirming the efficiency of the oral route of infection in mouse BSE.…”

mentioning

confidence: 99%

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PrPTSE in muscle-associated lymphatic tissue during the preclinical stage of mice infected orally with bovine spongiform encephalopathy

Cardone

Thomzig

Schulz‐Schaeffer

et al. 2009

Journal of General Virology

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The involvement of muscles in the pathogenesis of transmissible spongiform encephalopathies (TSEs) is irregular and unpredictable. We show that the TSE-specific protein (PrP TSE ) is present in muscles of mice fed with a mouse-adapted strain of bovine spongiform encephalopathy as early as 100 days post-infection, corresponding to about one-third of the incubation period. The proportion of mice with PrP TSE -positive muscles and the number of muscles involved increased as infection progressed, but never attained more than a limited distribution, even at the clinical stage of disease. The appearance of PrP TSE in muscles during the preclinical stage of disease was probably due to the haematogenous/lymphatic spread of infectivity from the gastrointestinal tract to lymphatic tissues associated with muscles, whereas in symptomatic animals, the presence of PrP TSE in the nervous system, in neuromuscular junctions and in muscle fibres suggests a centrifugal spread from the central nervous system, as already observed in other TSE models.

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supporting

confidence: 88%

mentioning

confidence: 94%

mentioning

confidence: 98%

mentioning

confidence: 99%

mentioning

confidence: 99%

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PrPTSE in muscle-associated lymphatic tissue during the preclinical stage of mice infected orally with bovine spongiform encephalopathy

Cardone

Thomzig

Schulz‐Schaeffer

et al. 2009

Journal of General Virology

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Variante Creutzfeldt-Jakob-Krankheit

2005

Bundesgesundheitsbl - Gesundheitsforsch - Gesundheitsschutz

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Mit tei lun gen des Ar beits krei ses Blut des Bun des mi nis te ri ums für Ge sund heit und So zia le Si che rung Va ri an te Creutz feldtJa kob-Krank heitStel lung nah men des Ar beits krei ses Blut des Bun des mi nis te ri ums für Ge sund heit und So zia le Si che rung Der Ar beits kreis Blut des Bun des mi niste ri ums für Ge sund heit und So zia le Si cherung gibt als na tio na les Be ra tungs gre mium Stel lung nah men zu neu ar ti gen Er regern ab, be wer tet neue Er kennt nis se zu bekann ten Er re gern und er ar bei tet ent sprechen de Emp feh lun gen für die Fachöf fentlich keit. Die se Se rie von Stel lung nah men zu ein zel nen Er re gern wird als Zu sam menfas sung des ak tu el len Wis sens stan des veröf fent licht, spe zi ell un ter trans fu si ons medi zi nisch re le van ten Aspek ten (Bun des gesund heits bl., 41,53, 1998).Frü he re Bei trä ge be fass ten sich mit der Creutz feldt-Ja kob-Er kran kung, dem Parvo vi rus B19 und dem GB-Vi rus Typ C (He pa ti tis-G-Vi rus) (alle Bun des ge sundheits bl. 41, [78][79][80][81][82][83][84][85][86][87][88][89][90] 1998), HTLV-I/-II (Bundes ge sund heits bl. 41, 512-517, 1998), Yersi nia en tero co li ti ca (Bun des ge sund heitsbl. 42, 613-621, 1999), TT-Vi rus (Bun desge sund heits bl. 43, 154-156, 2000), He pa titis-B-Vi rus (HBV) (Bun des ge sund heits bl. 43, 240-248, 2000) und Hu ma nes Cy to mega lo vi rus (HCMV) (Bun des ge sund heitsbl. 43, 653-659, 2000), He pa ti tis-A-Vi rus (Bun des ge sund heits bl. 44, 844-850, 2001), Tre po ne ma pal li dum (Bun des ge sund heitsbl. 45, 818-826, 2002), He pa ti tis-C-Vi rus (Bun des ge sund heits bl. 46, 712-722, 2003), Hu ma nes Im mun schwä che vi rus (HIV) (Bun des ge sund heits bl. 47, 83-95, 2004), Ar bo vi ren -durch Ar thro po den über tragba re Vi ren (Bun des ge sund heits bl. 47, 910-918, 2004) und Co xi el la bur ne tii -Er re ger des Q-(que ry) Fie bers (Bun des ge sundheits bl. 48, 814-821, 2005).GSS Krank heits be ginn zwi schen 50 und 60 Jah ren, fa mi li äre Häu fung, ze re bel lä re Ata xie, sel te ner De menz zu Be ginn, lang sa me Pro gres si on (5 Jah re bis Tod); Häu fig keit 1 in 18 Mil lio nen. Ia tro ge ne CJK Krank heits be ginn ca. 10 Jah re nach Ex po si ti on, Ver lauf ver gleich bar zur spon ta nen CJK bei neu ro na lem In fek ti ons weg und ver gleich bar zu GSS bei in tra mus ku lä rer In fek ti on (z. B. durch Wachs tums hor mo ne). KuruKrank heits be ginn ca. 5-7 Jah re nach ora ler Auf nah me, ze re bel lä re Ata xie, Ver hal tens än de run gen, De menz im Spät sta di um, Myo klo nus.vCJK Al ter bei Krank heits be ginn 11-72 (im Mit tel=28), psy chi at ri sche Auf fäl lig kei ten, Dys äs the si en, pro gres si ve ze re bel lä re Dys funk ti on, De menz, Myo klo nus, in der Re gel lang sa mer Krank heits ver lauf.

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The synaptic pathology of α-synuclein aggregation in dementia with Lewy bodies, Parkinson’s disease and Parkinson’s disease dementia

2010

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Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) are usually associated with loss of dopaminergic neurons. Loss of substantia nigra neurons and presence of Lewy body inclusions in some of the remaining neurons are the hallmark pathology seen in the final stages of the disease. Attempts to correlate Lewy body pathology to either cell death or severity of clinical symptoms, however, have not been successful. While the pathophysiology of the neurodegenerative process can hardly be explained by Lewy bodies, the clinical symptoms do indicate a degenerative process located at the presynapse resulting in a neurotransmitter deficiency. Recently it was shown that 90% or even more of α-synuclein aggregates in DLB cases were located at the presynapses in the form of very small deposits. In parallel, dendritic spines are retracted, whereas the presynapses are relatively preserved, suggesting a neurotransmitter deprivation. The same α-synuclein pathology can be demonstrated for PD. These findings give rise to the notion that not cell death but rather α-synuclein aggregate-related synaptic dysfunction causes the neurodegeneration. This opens new perspectives for understanding PD and DLB. If presynaptic α-synuclein aggregation, not neuronal loss, is the key issue of the neurodegenerative process, then PD and DLB may eventually be treatable in the future. The disease may progress via trans-synaptical spread, suggesting that stem cell transplants are of limited use. Future therapies may focus on the regeneration of synapses.

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

Cited by 55 publications

References 35 publications

PrPTSE in muscle-associated lymphatic tissue during the preclinical stage of mice infected orally with bovine spongiform encephalopathy

PrPTSE in muscle-associated lymphatic tissue during the preclinical stage of mice infected orally with bovine spongiform encephalopathy

Variante Creutzfeldt-Jakob-Krankheit

The synaptic pathology of α-synuclein aggregation in dementia with Lewy bodies, Parkinson’s disease and Parkinson’s disease dementia

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