NR AXMG
AU Ferrer,I.; Rodriguez,A.; Siso,S.; Gonzalez,L.; Chianini,F.; Jeffrey,M.
TI Neuromodulatory Responses Do not Match Degenerative Changes in Natural Scrapie
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.134
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
Morphological abnormalities in the brains of natural scrapie cases, namely astrocytic gliosis, spongiform change and disease-associated PrP (PrPd) deposition were analysed in parallel with biochemical changes related with the expression of aquaporins 1 and 4 (AQP1, AQP4), and metabotropic glutamatergic receptors type I (mGluR1) and adenosine receptors type I (A1R). Immunohistochemistry for glial fibrillary acidic protein (GFAP) and PrPd, and gel electrophoresis and western blotting for AQP1, AQP4, mGluR1, phospholipase C ß1 (PLCß1), normal protein kinase Cg (nPKCg), protein Gaq (Gaq), A1R and adenyl cyclase1 (AC1) were performed in frontal cortex, striatum, thalamus, hypothalamus, cerebellum (vermis) and obex of five scrapieaffected sheep and four healthy sheep controls. PrPd deposition was found in all regionsexamined from sheep scrapie; spongiform degeneration occurred in the striatum, thalamus, hypothalamus, vermis and obex; severe astrocytic gliosis was mainly present in the thalamus, hypothalamus and obex; AQP1 expression levels were found to be elevated in the striatum (p<0.05) and AQP4 levels in the striatum (p<0.01) and obex (p<0.05). No significant differences in the expression levels of mGluR1, and Gaq in any brain region, but reduced PLCß1 was observed in the striatum, thalamus and obex (p<0.05) while PKC in the obex only (p<0.05). Finally, A1R levels were significantly increased in the striatum only, whereas no modifications in the expression levels of AC1 were found in any region. These results may predict reduced mGLuR1
signalling in the striatum, thalamus and obex, and up-regulation of protective A1R
signals in the striatum in natural scrapie. Although these findings point towards the involvement of AQPs, and mGluR1 and AR pathways in natural scrapie, it is clear that abnormalities converge in some affected regions but not in all of them thus suggesting
independent regulatory factors for the distinct degenerative and neuroprotective responses.
AD I. Ferrer, A. Rodriguez, IDIBELL-Hospital Universitari de Bellvitge, Institut de Neuropatologia, Spain; S. Siso, L. Gonzalez, M. Jeffrey, Pentlands Science Park, Veterinary Laboratories Agency (VLA-Lasswade), UK; F. Chianini, PSP, Moredun Research Institute, UK
SP englisch
PO Schottland