NR AXJW
AU Brown,K.L.; Wathne,G.J.; McBride,P.; Bruce,M.E.; Mabbott,N.A.
TI Transmissible Spongiform Encephalopathy (TSE) Pathogenesis is Impaired in Aged Mice
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.32
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
Since variant CJD (vCJD) was first identified there have been almost 200 cases of the disease worldwide, the majority of which have occurred in the United Kingdom (UK). As it is probable that a large percentage of the UK population were exposed to bovine spongiform encephalopathy (BSE) at the height of the epidemic, it is important to determine why the disease has occurred predominantly in young individuals.
The possibility that young adults were exposed to greater levels of BSE by dietary preference has not been substantiated, suggesting that factors related to age, e.g. immunosenescence, may influence susceptibility to infection. Indeed, epidemiological evidence suggests that most cattle were infected with BSE as calves and studies of natural sheep scrapie suggest that lambs may be more susceptible to infection than adults. The capacity of the immune system to mediate immune responses to pathogens declines with age. A number of studies have shown that this decline in immune function is related to alterations in lymphocyte and follicular dendritic cell (FDC) function. As FDCs are critically involved in the pathogenesis of many TSEs age related effects on immune function may influence pathogenesis.
To examine age related influences on TSE infection we aged mice to approximately two thirds of their natural lifespan (600 days) and injected them peripherally (orally or intraperitoneally), or intracerebrally with the ME7 strain of scrapie. Studies in mice have shown that FDC function is impaired at this age. All of the intracerebrally injected aged mice developed both clinical and pathological signs of scrapie. None of the peripherally challenged aged mice developed clinical disease; however vacuolar degeneration in brain was detected in 33% of intraperitoneally and 42% of orally challenged mice. In addition, infectivity levels in lymphoid tissues from aged mice were substantially lower than those of the young mice. We suggest that this impaired pathogenesis coincides with reduced immune function and provides evidence that immunosenescence may influence TSE pathogenesis.
AD K.L. Brown, G.J. Wathne, P. McBride, M.E. Bruce, N.A. Mabbott, Neuropathogenesis Unit, Roslin Institute, UK
SP englisch
PO Schottland
EA pdf-Datei und Poster (Posterautoren: K.L. Brown, G. Wathne, N.A. Mabbott und M.E. Bruce; Postertitel: The effect of age on TSE pathogenesis)