NR ATGX
AU Coulpier,M.; Messiaen,S.; Hamel,R.; Fernandez de Marco,M.; Lilin,T.; Eloit,M.
TI BAX-independent neuronal death in experimental BSE
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Cell Biology of PrPc and PrPsc CELL-03
PT Konferenz-Poster
AB Neuronal death is a pathological hallmark of prion diseases. Yet, the mechanisms by which neurons die are poorly understood. Apoptosis, a programmed form of cell death, has been described in the brains of patients affected with Creutzfeldt-Jakob Disease (CJD), Fatal Familial Insomnia (FFI) and in scrapie-infected hamsters, mice and sheeps. One of the major pro-apoptotic protein, BAX, was shown to play a central role in neuronal death in diverse situations including in a transgenic model of inherited prion disease. However its role in prion disease of infectious origin is still not known. Here, using mice knocked out for the Bax gene, we investigated BAX implication in neuronal death induced by infectious prion. A BSE mouse-adapted prion strain (6PB1) was inoculated to Bax -/- mice and their wild-type littermates. Terminal stage of the disease occurred about 19 weeks post-inoculation in wild-type mice. Brains of infected animals showed a strong astrogliosis and an accumulation of PrPres, the pathological isoform of the cellular prion protein PrPc. None of these clinical and biochemical properties were altered in Bax -/- mice. Most of all, the spongiform changes and degeneration of neurons in hippocampus and thalamus, characterizing brains of 6PB1-infected mice, were not prevented by Bax deletion. Our findings demonstrate that neuronal death induced by the BSE-prion strain occurs by a BAX-independent pathway. They reveal the existence of multiple molecular pathways for neuronal death in prion disease and suggest that infectious and genetic prion disease do not share a common pathway of neurodegeneration.
AD M.Coulpier, S.Messiaen, R.Hamel, T.Lilin, M.Eloit, Ecole Vétérinaire de Maisons-Alfort, France; M.Fernandez de Marco, Universidad de Cordoba, Spain
SP englisch
PO Deutschland