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Title: An investigation of scrapie pathogenesis in neonatal mice with special reference to germinal centre maturation
Author: Ierna, M. X.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2002
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In adult mice, cellular prion protein (PrPc) expressing follicular dendritic cells (FDCs) in the spleen are required for replication of scrapie after i.p challenge. It is therefore hypothesised that neonatal mice resist scrapie infection due to a lack of mature PrPc expressing FDCs within spleen. The presence of PrPc and the maturation of FDCs were studied in the spleens of developing mice using immunocytochemistry and confocal microscopy. It was found that FDC-M1+ cells can be detected from birth within immature spleen white pulp. However detectable levels of the FDC functional marker, complement receptor 1, were not observed until 14 days after birth, inferring that the FDCs are functionally immature prior to this age. PrPc was detected from 10 days old immunocytochemically, and was found to co-localise with morphologically immature FDC-M1+ cells compared to 30 day old mice. It can be concluded that PrPc is expressed on immature FDCs in the 10 day old mouse. The detection of PrPc on FDC-M1+ cells between 10 and 14 days coincides with a dramatic increase in susceptibility to scrapie. This is consistent with the hypothesis that neonatal mice have an impaired ability to replicate scrapie due insufficient PrPc expressing FDCs in the spleen. Paradoxically, previous experiments have also shown that a proportion of peripherally inoculated neonatal mice develop scrapie after very short incubation periods ranging between 150-230 days. During the first two weeks of life, the number of cases with short incubation periods decreases. It is hypothesised that due to the immaturity of peripheral nerves at birth, infectivity can be taken up more efficiently by neonatal peripheral nerve endings and reach the central nervous system (CNS) without prior replication in the spleen.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available