NR ATOZ
AU Knox,J.D.; Boreham,D.R.; Czub,S.; Wyatt,H.; Parchaliuk,D.; Ramdoo,B.; Mitchel,R.E.
TI Prion Disease Incubation Period Prolonged by Radiation
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Pathogenesis PATH-10
PT Konferenz-Poster
AB The accumulation of PrPres correlates with disease progression and coincides with the appearance of markers of oxidative stress and a dramatic reduction in the activity of the anti-oxidant systems of the brain. These observations support the suggestion that oxidative stress is in part responsible for the disease-associated neurodegeneration. Low-dose radiation is known to induce enzymatic and non-enzymatic oxidative stress response systems. Previously, we have demonstrated that in C57/BL6 mice intra-cerebrally infected with the prion strain ME7, four exposures of 60Co-g radiation (500 mGy/fraction) up to 50 days post inoculation significantly prolonged the period of disease incubation. We suspect that the induction of anti-oxidant systems by the radiation exposure in advance of the oxidative stress brought about by the accumulation of PrPres was responsible for the increased incubation period observed. To further investigate the mechanism by which radiation modulates prion disease progression we have collected brain samples at six time points post-infection and post-treatment. These samples have been analyzed using an oligonucleotide microarray. The changes in gene expression elicited by the radiation treatments in infected animals were transient with the bulk of the changes only apparent immediately after radiation exposure. Conversely, an immunohistochemical examination of a parallel set of brain samples demonstrated that the radiation-induced delay in the accumulation of the hallmarks of disease progression only becomes apparent at late stages of the disease. The activation of a protective mechanism in a subset of cells whose presence only becomes apparent when the level of cumulative damage (as measured in untreated mice) becomes substantial is consistent with this observation.
AD J.David Knox, Debra Parchaliuk, Brendon Ramdoo, Public Health Agency of Canada; Douglas R. Boreham, McMaster University, Canada; Stephanie Czub, Canadian Food Inspection Agency; Heather Wyatt, Ron E. Mitchel, Atomic Energy of Canada Ltd.
SP englisch
PO Deutschland