NR ABDG
AU Beck,E.; Daniel,P.M.; Davey,A.J.; Gajdusek,D.C.; Gibbs,C.J.Jr.
TI The pathogenesis of transmissible spongiform encephalopathy: an ultrastructural study.
QU Brain: A Journal of Neurology 1982 Dec; 105 (4): 755-86
PT journal article
AB The brains of 9 spider monkeys, inoculated intracerebrally with brain suspension from kuru patients and of 3 normal control monkeys have been studied. All the animals were killed by perfusion with fixative, 8 during early incubation (ranging from 2 to 40 weeks) when healthy and free from neurological signs, one after 122 weeks when the disease was fully established. The most striking feature seen in every brain between the incubation times of 4 and 40 weeks was the formation of multilaminated membranes (ACPMs). These affected stretches of two apposed, mostly neuronal, plasma membranes over variable distances and created the impression of complex ribbon-or cord-like junctions. Their number varied with the length of incubation, reaching a peak at 13 weeks and declining thereafter. ACPMs were found throughout the grey matter, but they were most numerous in phylogenetically older regions of the brain, regions which also show the severest lesions in human kuru. It is suggested that ACPMs are initially due to an excessive synthesis of some membrane constituent by the perikaryon and various possibilities for their genesis are discussed. The hypothesis is advanced that they may be due to the reactivation of embryonic growth mechanisms and represent abortive junctions which, being formed in mature neurons, take a rather bizarre shape. Other changes such as the formation of somatic spines, an excessive number of dendritic spines including a high proportion with long tortuous necks, and the presence of binucleated neurons and numerous growth cones, point to the similarly immature pattern and would support this hypothesis. The material provided ample evidence that ACPMs, which can occupy as much as 26 per cent of a dendritic surface, give rise to intracytoplasmic vacuoles, which may therefore be regarded as secondary to a primary change in the permeability of the plasma membrane at the site of ACPMs. Individual single vacuoles could often build up into complex soap-bubble-like arrays, which were interpreted as the ultrastructural equivalent of histological status spongiosus. There is some evidence that the development of status spongiosus in other transmissible spongiform encephalopathies follows the same pattern.
IN Kuru ließ sich durch intrazerebrale Inokulation von Gehirnsuspensionen auf Klammeraffen übertragen. Als Negativkontrolle dienten Gehirnsuspensionen gesunder Affen. 8 der infizierten Affen wurden bereits 2-40 Wochen nach der Infektion symptomfrei getötet, der 9. Affe wurde nach 122 Wochen getötet, als er bereits voll erkrankt war. Die auffälligste Beobachtung bei den nach 4-40 Monaten getöteten Affen waren mehrschichtige Membranen. Die Zahl dieser verklebten Flächen benachbarter Membranen nahm bis zur 13. Woche zu und danach wieder ab. Sie kamen überall in der grauen Hirnsubstanz vor, waren aber am häufigsten in den phylogenetisch ältesten Hirnstrukturen. Dort wurden auch die größten Schädigungen in Kuru-Gehirnen gefunden. Es wurden auch Ausstülpungen auf den Zellkörpern und Dendriten, zweikernige Neuronen und viele Wachstumsausstülpungen beobachtet. Diese strukturellen Veränderungen gehen in die Richtung embryonaler Wachstumsprozesse.
MH Animal; Brain/*ultrastructure; Cebidae; Cell Membrane/ultrastructure; Cell Membrane Permeability; Cerebellar Cortex/ultrastructure; Cerebral Cortex/ultrastructure; Corpus Striatum/ultrastructure; Disease Models, Animal; Female; Kuru/etiology/*pathology/transmission; Male; Neurons/ultrastructure; Organoids/ultrastructure
SP englisch
PO England