NR AXJV
AU Brown,D.A.; Ironside,J.W.; Fraser,J.R.; Tuzi,N.L.
TI Cytoskeletal Disruption and the Role of The MAP Kinase Pathways in Two Neuronal Loss Models of Murine Scrapie
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.173
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB One of the characteristic pathological changes observed in transmissible spongiform encephalopathies (TSEs) is neuronal loss. Studies in experimental mouse scrapie models suggest that neurons die through an apoptotic mechanism, which may be related to early cytoskeletal disruption. In this study two contrasting scrapie mouse models were used: the ME7/CV model in which neuronal loss is targeted to CA1, and the 87V/VM model, where neurodegeneration targets the CA2 of the hippocampus. Using immunocytochemical and Western blot techniques the distribution of cytoskeletal proteins MAP2 (microtubule associated protein 2) and tubulin, and the expression of mitogen activated protein kinases (MAPKs) and their role in the cytoskeletal disruption were investigated . Results have shown MAP2 and tubulin immunoreactivity to be decreased in both scrapie models, whilst an increase in the the phosphoylated form of the MAP kinase ERK1/2 was observed in both models, and phosphorylated P38MAPK was increased in the ME7/CV model. The MAP Kinases in their phosphorylation state can switch on or off the activity of substrate proteins, such as cytoskeletal proteins. The increase in phosphorylated MAP kinases, observed in both scrapie mouse models, may in turn lead to the decrease in MAP2, destabilization of microtubules and subsequent loss of tubulin. These results suggest that neuronal death may be mediated by cytoskeletal damage, but further studies are now underway to identify the details of the relationship.
AD D. Brown, J.R. Fraser, N.L. Tuzi, Neuropathogenesis Unit, Roslin Institute, UK; J.W. Ironside, CJD Surveillance Unit, Western General Hospital, UK
SP englisch
PO Schottland