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Study Of Changes Of Neuropathology And Neuro-proteins In The Brains Of The Hamsters Infected With Scrapie Strain 263K And The Cell Apoptosis Induced By The Recombinant Aglycosyl Human PrP In Vitro

Posted on:2006-01-30Degree:DoctorType:Dissertation
Country:ChinaCandidate:L ChenFull Text:PDF
GTID:1104360185473630Subject:Biochemistry and Molecular Biology
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Prion diseases are a group of transmissible neurodegenerative encephalopathies involved in human and animals. Since the emerging of bovine spongiform encephalopathy and variant Creutzfeldt-Jacob disease (vCJD), the threat of prion diseases on public health became increasingly remarkable. The pathogen of this kind disease is believed to be a unique infectious protein particle devoid of nucleic acid.Among several transmitting pathways, blood-borne way plays very important role in acquired human CJD. More recently, it has been confirmed that vCJD could be transmitted from men to men through blood transfusion. In order to compare the differences in the clinical characteristics, neuropathology, PrP molecular isoform and other neuro-proteins among the scrapie experimental animals induced through blood transmission and direct central nerve inoculation, 5 μl scrapie agents (8.2-log10 LD50 i.c. units /0.001g brain) were injected into two-week old golden hamsters intracerebrally and intracardiacly, respectively, while 100 μl scrapie agents were injected intramuscularly. With these infectious dosages, all intracardiacly infected hamsters (7/7) showed the typical manifestations of experimental scrapie, with the mean incubation of 90±11.5 days similar to that of intracerebrally infected hamsters (91.5±20.5 days). However, the clinical courses of intracardiacly infected hamsters were slightly longer than that of intracerebrally infected ones. Scrapie experimental manifestations were induced in all intramuscularly infected animals (8/8), with the mean incubation of 69.2±2.8 days that was comparable with the data from intracerebrally infected hamsters in our previous study. Neuropathological analyses revealed the typical spongiform degeneration and deposits of PrPSc in various brain regions, among them brain stem was the mostly affected area. Western blot assays identified protease-resistant PrP signals in the brain homogenates from all infected animals. No significant differences have been observed among the three infectious pathways. These results indicate again that the blood-borne animal model of scrapie has been established and the prion infectious agents can easily transmitted through blood pathway.
Keywords/Search Tags:prion diseases, scrapie 263K strain, transmission pathway, animal model, neuropathology, bioassay, prion protein (PrP), N-glycosylation, cell apoptosis, Bcl-2
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