The pathogenesis of transmissible spongiform XXXX : an ultrastructural study.

@entity1 @entity602 @entity75 @entity159
The brains of 9 spider monkeys, inoculated intracerebrally with brain suspension from kuru @entity1 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 @entity602 . 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 @entity1 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 @entity159 . There is some evidence that the development of @entity159 in other transmissible spongiform @entity75 follows the same pattern.
