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Clustering of PrPres in Central Brain Regions of Macaques

flounder

Well-known member
Subject: Clustering of PrPres in Central Brain Regions of BSE-infected
Macaques
Date: September 29, 2007 at 12:42 pm PST

P03.138


Clustering of PrPres in Central Brain Regions of BSE-infected Macaques


(M. Fascicularis) Motzkus, D1; Montag, J1; Hunsmann, G1; Schulz-Schaeffer,
W2
1German Primate Center, Dept. Virology and Immunology, Germany; 2University
of Göttingen, Dept. Neuropathology, Germany


According to biochemical and epidemiological findings bovine spongiform
encephalopathy (BSE) was transmitted to humans causing variant Creutzfeldt
Jakob disease (vCJD). Previous studies have shown intracerebral (i.c.)
transmission of BSE affected brain from cattle can cause TSEs in cynomolgus
macaques (M. fascicularis). The lesion profile resembles that of vCJD.
Recently, oral infection of M. fascicularis with macaque-adapted BSE
material was reported. In cooperation with five European partners a
quantitative study for the transmission of the BSE agent to M. fascicularis
was initiated to assess the risk of vCJD infection in humans through
contaminated food products (EU study QLK1-CT-2002-01096). Titration was
performed orally and intracerebrally to determine the minimal infectious
dose for cynomolgus monkeys. Here we report the outcome of the intracerebral
infection with 50 mg BSE brain homogenate in six non-human primates. All
animals showed clinical symptoms of TSE after an average of 1100 days. Using
immunohistological and biochemical methods prion protein (PrP) deposits were
confirmed in the brains of all animals. Using Western blot analysis the
glycosylation pattern was compared to the inoculum and to the pattern of
different CJD subtypes. Simian PrPres was detected with the monoclonal anti
prion antibody 11C6, which revealed a higher sensitivity in comparison to
12F10
and 3F4. We found that the PrP glycopattern in BSE-infected cynomolgus
macaques resembles human CJD type 2. We further analysed the distribution of
PrPres by microdissection of seven different brain regions of all infected
macaques. High concentrations of PrPres were detected in central brain
regions, as gyrus cinguli,
nucleus caudatus, vermis cerebelli and basis pontis. In contrast, in the
peripheral regions gyrus frontalis, gyrus parietalis and gyrus occipitalis
PrPres was hardly detectable. Thus, the incubation period related to the
life expectancy, the PrPres glycosylation pattern as well as the
distribution in certain brain regions resemble those in vCJD patients. The
relative abundance of PrPres in macaques will be compared to that of orally
infected animals.


http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf


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