NR AFZE
AU Jeffrey,M.J.; Halliday,W.G.; Bell,J.; Johnston,A.R.; MacLeod,N.K.; Ingham,C.; Sayers,A.R.; Brown,D.A.; Fraser,J.R.
TI Synapse loss associated with abnormal PrP precedes neuronal degeneration in the scrapie-infected murine hippocampus
QU Neuropathology and Applied Neurobiology 2000 Feb; 26(1): 41-54
PT journal article
AB Numbers of neurones, synapses and axon terminals were quantified in a murine scrapie model with severe hippocampal pyramidal cell loss, in which definite clinical scrapie is evident from 226 days post-infection (dpi) and death occurs around 250 dpi. Disease-specific PrP accumulations were first seen at 70 dpi (28% of the incubation period (IP)) in thalamus and as sparse foci within the stratum pyramidale of CA1. By 98 dpi (39% IP), PrP was seen in the stratum radiatum and was found at later stages throughout all levels of the hippocampus. At the ultrastructural level in the stratum radiatum of CA1, a decrease in the numbers of simple synapses from 84 dpi (34% IP) and in perforated synapses from 98 dpi (42% IP) was found using an unbiased stereological method, the disector analysis. Degeneration of axon terminals was found from 98 dpi (39% IP) onwards. Neuronal loss was detected in CA1 from 180 dpi (72% IP). The results suggest that the fundamental lesion in the hippocampus of ME7-infected mice is associated with PrP release from CA1 pyramidal neurones, which perturbs synaptic function and leads to degeneration of preterminal axons, and that subsequent pathological changes including neurone loss are sequelae to this initial insult.
MH Animal; Astrocytes/pathology; Cell Count; Hippocampus/chemistry/*pathology; Mice; Mice, Inbred C57BL; Microscopy, Electron; Nerve Degeneration/*pathology; Neurons/chemistry/ultrastructure; Neutrophils/pathology; Prions/*analysis; Scrapie/*pathology; Support, Non-U.S. Gov't; Synapses/*pathology/ultrastructure; Vacuoles/pathology/ultrastructure
AD Martin J. Jeffrey (m.jeffrey@vla.maff.gov.uk), W. G. Halliday, VLA Lasswade Veterinary Laboratory, Pentlands Science Park, Bush Loan, Penicuik, Edinburgh EH26 OPZ, Scotland, UK; J. Bell, Debbie A. Brown (debbie.brown@bbsrc.ac.uk), Janet R. Fraser (janet.fraser@bbsrc.ac.uk), Institute for Animal Health, BBSRC and MRC, Neuropathogenesis Unit, Ogston Building, West Mains Road, Edinburgh EH9 3JF, Scotland, UK; A. R. Johnston, N. K. Macleod, Physiology Department, Edinburgh University; C. Ingham, Department of Preclinical Veterinary Science, Edinburgh University, UK; A. R. Sayers, VLA Weybridge, Surrey
SP englisch
PO England