NR ANQD
AU Ersdal,C.; Simmons,M.M.; Goodsir,C.M.; Martin,S.; Jeffrey,M.J.
TI Sub-cellular pathology of scrapie: coated pits are increased in PrP codon 136 alanine homozygous scrapie-affected sheep.
QU Acta Neuropathologica 2003 Jul; 106(1): 17-28
PT journal article
AB Sub-cellular studies of transmissible spongiform encephalopathies (TSEs) have been carried out on several animal species and human beings. However, studies of optimal perfusion-fixed tissues have largely been confined to examination of rodents. Using a recently developed technique, heads of scrapie-affected sheep and controls were perfusion fixed with mixed aldehydes. The obexes were immunohistochemically labelled with PrP antibodies, and the dorsal motor nucleus of the vagal nerve was examined by electron microscopy. Irregular neuritic profiles with highly invaginated membranes, associated with coated pits were found in all scrapie-affected sheep, but not in controls. Interestingly, they were consistently more frequent in the homozygous A(136) sheep. This is the first report describing sub-cellular differences in pathology associated with different PrP genotypes. Rarely, amorphous material, or sparse fibrillar structures, were present in the extracellular space. The changes were often associated with irregular plasmalemma and frequent coated pits. Vacuolation typical of TSEs, dystrophic neurites and variable gliosis were present. Herniation of membranes and organelles from apparently healthy processes into adjacent vacuoles and dendrites was also observed. We suggest that the increase in coated pits and plasmalemma invagination is related to an attempted internalisation of aggregated disease-specific PrP, or protofilaments, from the extracellular space.
MH ATP-Binding Cassette Transporters/genetics/*metabolism/ultrastructure; Alanine/*genetics; Animal; Coated Pits, Cell-Membrane/*metabolism/pathology/ultrastructure; Comparative Study; Homozygote; Immunohistochemistry; Microscopy, Electron/methods; Myelin Sheath/metabolism/pathology/ultrastructure; Neuroglia/metabolism/pathology/ultrastructure; Neurons/metabolism/pathology/ultrastructure; Neuropil/metabolism/pathology/ultrastructure; Olivary Nucleus/metabolism/pathology/ultrastructure; Peptide Fragments/immunology/metabolism/ultrastructure; Scrapie/genetics/*pathology; Sheep; Sheep Diseases/*pathology; Subcellular Fractions/metabolism/pathology/ultrastructure; Support, Non-U.S. Gov't; Vacuoles/metabolism/pathology/ultrastructure
AD Cecilie Ersdal (cecilie.ersdal@veths.no), Department of Sheep and Goat Research and Department of Morphology, Genetics and Aquatic Biology, The Norwegian School of Veterinary Science, 0033 Oslo, Norway; Marion M. Simmons, Neuropathology Unit, Veterinary Laboratories Agency-Weybridge, New Haw, Addlestone, Surrey, KT15 3NB, UK; Caroline M. Goodsir, Stuart Martin, Martin J. Jeffrey (m.jeffrey@vla.maff.gov.uk), VLA Lasswade Veterinary Laboratory, Pentlands Science Park, Bush Loan, Penicuik, Edinburgh EH26 OPZ, Scotland, UK
SP englisch
PO Deutschland