NR AXUY
AU Rangel,A.H.; Burgaya,F.; Gavin,R.; Soriano,E.; Aguzzi,A.; Del Rio,J.A.
TI Enhanced Susceptibility of Prnp-Deficient Mice to Kainate-Induced Seizures, Neuronal Apoptosis, and Death: Role of AMPA/Kainate Receptors
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Natural and Experimental Strains P02.28
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB The normal physiological functions of the cellular prion protein (PrPc) are still elusive. This GPI-anchored protein exerts many functions, including roles in neuron proliferation, neuroprotection or redox homeostasis. However, there are conflicting data concerning its role in synaptic transmission. While several studies report that PrPc participates in NMDA-mediated neurotransmission, parallel studies describe normal behaviour of PrPc-mutant mice. However, abnormal axon connections have been described in the dentate gyrus of the hippocampi of PrPc-deficient mice similar to those observed in epilepsy. Indeed, a report indicates increased susceptibility to kainate (KA) in these mutant mice. Here we extend the observation of these studies by means of several histological and biochemical analyses of KA-treated mice. PrPcdeficient mice showed increased sensitivity to KA-induced seizures in vivo and in vitro in organotypic slices. In addition, we demonstrate that this sensitivity is cell specific since interference experiments to abolish PrPc expression increased susceptibility to KA in PrPc-expressing cells. Finally, we indicate a correlation of susceptibility to KA in cells lacking PrPc with the differential expression of GluR6 and GluR7 KA receptor subunits using real-time RT-PCR methods. Taken together, these results indicate that PrPc exerts a neuroprotective role against KA-induced neurotoxicity, probably by regulating the expression of KA receptor subunits.
AD A.H. Rangel, J.A. Del Rio, University of Barcelona, Cell Biology, Spain; F. Burgaya, R. Gavín, E. Soriano, Institute for Research in Biomedicine of Barcelona, Cell Biology, Spain; A. Aguzzi, University Hospital of Zürich, Institute of Neuropathology, Switzerland
SP englisch
PO Schottland