NR AXYF
AU Vidal,E.; Tortosa,R.; Marquez,M.; Serafin,A.; Hidalgo,J.; Pumarola,M.
TI Infection of Metallothionein 1+2 Knockout Mice with RML Scrapie
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.69
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
Metallothioneins (MT) are heavy metal-binding, antioxidant proteins with relevant roles described in many pathological conditions affecting the central nervous system (CNS). Regarding prion diseases, a number of publications demonstrate an upregulation of MT-I+II in the brains of TSE affected cattle, humans and experimentally inoculated rodents. Since the prion protein also binds copper, and oxidative stress is one of the events presumably triggered by PrPsc deposition it seems plausible that MTs have a relevant role in the outcome of these neurodegenerative processes.
To gain knowledge of the role of MTs in TSE pathogeny, particularly of that of MT-I+II, a transgenic Mt1&2 knockout mouse model was intracerebrally inoculated with the mouse adapted Rocky Mountain Laboratory (RML) strain of scrapie; 129SvJ mice were used as controls (WT). Clinical signs were monitored and survival curves were drawn. Animals were humanely sacrificed when scored positive clinically. Brains were fixed following intracardiac perfusion with 4% formaldehyde, paraffin embedded, and processed for histological, histochemical and immunohistochemical evaluation.
The incubation period did not show significant differences between Mt1&2 KO and WT mice, nor did the evolution of neurological signs. Upon neuropathological characterisation of the mice brains moderate differences were observed regarding astroglial and microglial response, spongiosis score and PrPsc deposition, particularly in brain regions to which the studied strain showed a stronger tropism (i.e. hippocampus and thalamus). These differences might be a consequence of the lack of antioxidant protection usually given by MT-I+II in such a neuroinflammatory scenario in the CNS, and suggest that these MT isoforms afford a limited neuroprotection in this TSE model.
This study was financed by the Health Department of the Catalan Government (Departament de Salut, Generalitat de Catalunya).
AD E. Vidal, M. Pumarola, CReSA, Priocat Laboratory, Spain; R. Tortosa, A. Serafin, Veterinary Faculty, UAB, Animal Medicine and Surgery Department, Spain; M. Marquez, Veterinary Faculty, UAB, Animal Tissue Bank of Catalonia (BTAC), Spain; J. Hidalgo, UAB, Cellular Biology, Physiology and Immunology Dep., Spain
SP englisch
PO Schottland