NR AEOO
AU Giese,A.; Groschup,M.H.; Hess,B.; Kretzschmar,H.A.
TI Neuronal cell death in scrapie-infected mice is due to apoptosis
QU Brain Pathology 1995 Jul; 5(3): 213-21
PT journal article
AB Neuronal loss is a salient yet poorly understood feature in the pathology of transmissible spongiform encephalopathies (prion diseases). Cell culture experiments with neurotoxic prion protein fragments suggest that neuronal cell death in these diseases may be due to apoptosis. To test this hypothesis in vivo we used the in situ end-labeling (ISEL) technique and electron microscopy to study cell death in an experimental scrapie system in the mouse. ISEL, which relies on the incorporation of labeled nucleotides in fragmented DNA by terminal transferase, showed labeled nuclei in the brains and retinae of mice infected with the 79A strain of scrapie, whereas no labeling was observed in control animals. In the retina the highest numbers of labeled nuclei were found in the outer nuclear layer 120 days post infection followed by massive cell loss in this layer. In the brain, labeled nuclei were mainly found in the granular layer of the cerebellum of terminally ill mice. This corresponded to the presence of small dark nuclei with condensed and occasionally fragmented chromatin at the light and electron microscopical levels. Our results support the hypothesis that neuronal loss in spongiform encephalopathies is due to apoptosis. This may explain the almost complete absence of inflammatory response in prion diseases in the face of widespread neuronal cell death, and may also have therapeutic implications in the future.
IN Im Gegensatz zu normalen Gehirnen wurde in den Gehirnen und Netzhäuten scrapieinfizierter Mäuse kondensierte Chromosomen in kleinen, dunklen Zellkernen und Brüche in den DNAs gefunden. Dies scheint die Selbstmord-Hypothese als Erklärung für den Zelltod bei Prion-Krankheiten zu stützen.
ZR 42
MH Animal; Apoptosis/*physiology; Brain/pathology; Cerebellum/pathology; Disease Models, Animal; Female; Mice; Mice, Inbred C57BL; Microscopy, Electron; Neurons/*pathology; Retina/pathology; Scrapie/*pathology; Support, Non-U.S. Gov't
AD Department of Neuropathology, University of Göttingen, Germany.
SP englisch
PO Schweiz