NR AVKU
AU Coulpier,M.; Messiaen,S.; Hamel,R.; Fernandez de Marco,M.; Lilin,T.; Eloit,M.
TI Bax deletion does not protect neurons from BSE-induced death
QU Neurobiology of Disease 2006 Sep; 23(3): 603-11
PT journal article
AB Neurodegeneration is a common neuropathological feature of prion diseases. Although evidence of apoptosis was found in natural and experimental prion diseases, the precise mechanisms by which neurons die are poorly understood. The pro-apoptotic BAX protein, a key factor of the mitochondrial pathway, plays a central role in the regulation of neuronal apoptosis. Recently, BAX was implicated in neuronal death in a transgenic model of inherited prion disease. Nevertheless, whether neurodegeneration occurs by similar mechanisms in other prion diseases remains unknown. Here, using mice knocked out for the Bax gene, we investigated BAX implication in neuronal death induced by a prion disease of infectious origin. A mouse-adapted prion strain of bovine spongiform encephalopathy (BSE) was inoculated intracerebrally into Bax-/- mice and their wild-type littermates. We found that Bax inactivation did not alter the development of the disease. Clinical illness was not prevented. PrPres deposition and astrogliosis occurred to the usual extent. Neuronal integrity was not maintained, and neurons in hippocampus and thalamus were not protected. These results demonstrated that BAX is not necessary for neuron death induced by the BSE strain. They suggest the existence of multiple molecular death pathways in prion diseases.
MH Animals; Apoptosis/*genetics; Brain/*metabolism/pathology/physiopathology; Cattle; Disease Models, Animal; Encephalopathy, Bovine Spongiform/*genetics/physiopathology/*therapy; Female; Gene Therapy; Genetic Predisposition to Disease/genetics; Hippocampus/metabolism/pathology/physiopathology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Neurons/*metabolism/pathology; PrPsc Proteins/metabolism; Prions/metabolism; Research Support, Non-U.S. Gov't; bcl-2-Associated X Protein/*genetics
AD UMR Virologie 1161 INRA-AFSSA-ENVA, Ecole Nationale Veterinaire d'Alfort, 94704 Maisons-Alfort, France. mcoulpier@vet-alfort.fr
SP englisch
PO USA