NR AWKN
AU Montag,J.; Hunsmann,G.; Schulz-Schaefer,W.; Motzkus,D.
TI Clustering of PrPres in central brain regions of BSE-infected macaques (M. fascicularis)
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions RA-07
PT Konferenz-Poster
AB
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. 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 res subtypes. The glycopattern TSE infected cynomolgus macaques resembles human CJD type 2. Simian PrPres was detected with the monoclonal anti prion antibody 11C6, which revealed a higher sensitivity in comparison to 12F10 and 3F4. We further analysed the distribution of PrPres by microdissection of seven different brain regions of all infected macaques. High concentrations of PrPres were found 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.
AD J. Montag, G. Hunsmann, D. Motzkus: German Primate Center (DPZ), Dept. of Virology and Immunology, Kellnerweg 4, 37077 Göttingen, Germany; W. Schulz-Schaefer: Georg-August University Göttingen, Dept. of Neurology, Robert-Koch-Str. 40, 37075 Göttingen, Germany
SP englisch
PO Italien