Distinct spatial activation of intrinsic and extrinsic apoptosis pathways in natural scrapie: association with prion-related lesions.
Neurodegeneration and gliosis are the main neuropathological features of prion diseases. However, the molecular mechanisms involved in these processes remain unclear. Several studies have demonstrated changes in the expression of apoptotic factors and inflammatory cytokines in animals with experimental infection. Here we present the expression profiles of 15 genes implicated in the intrinsic and extrinsic apoptotic pathways in the central nervous systems of sheep naturally infected with scrapie. Expression changes obtained by real-time RT-PCR were also compared with the extent of classical scrapie lesions, such as prion deposition, neuronal vacuolisation, spongiosis, and astrogliosis as well as with the activation of caspase-3, using a stepwise regression. The results suggest that the factors assessed participate in apoptotic or inflammatory functions, depending on the affected area. The mitochondrial apoptosis pathway was associated with prion deposition in the prefrontal cortex (the less affected area), and with activation of caspase-3-mediated cell death via over-expression of BAK. In addition to its known association with astroglial activation, the extrinsic apoptosis pathway was also related to cell death and neuronal vacuolisation.
Serrano
Carmen
C
Laboratorio de Genética Bioquímica (LAGENBIO), Facultad de Veterinaria, Universidad de Zaragoza, Miguel Servet 177, 50013 Zaragoza, Spain.
Lyahyai
Jaber
J
Bolea
Rosa
R
Varona
Luis
L
Monleón
Eva
E
Badiola
Juan J
JJ
Zaragoza
Pilar
P
Martín-Burriel
Inmaculada
I
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D012313:RNA / Q000235:genetics; D012608:Scrapie / Q000378:metabolism / Q000473:pathology*; D012756:Sheep
D012313:RNA