NR AWGU
AU Heitz,S.; Bombarde,G.; Haeberle,A.M.; Vidal,C.; Vogel,M.; Deslys,J.P.; Bailly,Y.
TI Neither BAX knock-out nor BCL-2 overexpression modify brain pathology induced by scrapie prions in transgenic mice
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 PA-24
PT Konferenz-Poster
AB Although our understanding of prion diseases has greatly progressed over the last decade, the neurotoxic mechanisms triggered by prions in the mammalian brain remain unknown. The cellular prion protein is known to have antagonistic effects on mitochondrial apoptotic pathways by preventing pro-apoptotic BAX activation, thus mimicking the neuroprotective activity of BCL-2, a potent BAX inhibitor. By taking advantage of the strong tropism of the 22L scrapie prion strain for the cerebellum and the well known involvement of BAX and BCL-2 in several cases of apoptosis of cerebellar neurons, we analyzed the development of spongiform encephalopathy induced by the 22L strain of prion in the cerebrum and cerebellum of Bax knock-out mice, as well as in mice expressing a human Bcl-2 transgene (HuBCL-2). After infection with the 22L scrapie strain by either peripheral or intracerebellar routes, clinical illness developed in all cases and similar brain spongiosis profiles were displayed by both mutants and control wild-type mice at subterminal and terminal stages of the disease. In all mice, PrPsc immunohistochemical deposition patterns were similar throughout the brain including the cerebellum. Furthermore, no neuroprotective effects of Bax knock-out or of HuBcl2 were revealed by immunohistochemical staining for the Purkinje cell marker Calcium binding protein, the synaptic marker synaptophysin or the neuronal marker NeuN in the brain of the mutants. Finally, a similar pattern of astrocytosis was observed throughout the brain of infected mutants and wild-type mice. These results demonstrate that neuronal death induced by the 22L prion strain occurs by a BAX-independent pathway that cannot be antagonized by increasing the expression level of the anti-apoptotic factor BCL-2. Sponsored by GIS Prions.
AD S. Heitz, G. Bombarde, A.-M. Haeberlé, Y. Bailly: INCI UMR7168 CNRS Université Louis Pasteur Strasbourg France; C. Vidal, J.-P. Deslys: CEA/DSV/DRM/GIDTIP Fontenay-aux Roses France; M. Vogel: Maryland Psychiatric Research Center, University of Maryland Baltimore MA, USA
SP englisch
PO Italien