Light and electron microscopic studies of the 139A-H strain of scrapie passaged in hamsters

Abstract

We report here the light and electron microscopic neuropathology of the 139A-H strain of scrapie passaged in Syrian golden hamsters. The general neuropathological picture consisted of the spongiform change and severe astrocytic gliosis. The topography of prion protein (PrP) was variable, the highest signal was observed in the CA2-molecular layer, CA1-pyramidal and entorhinal cortex. The electron microscopy consisted of: 1. Spongiform vacuoles-these are always membrane bound and contain secondary vacuoles (i.e. membrane-bound compartments or vesicles within vacuoles) and curled membraned fragments. 2. Tubulovesicular structures (TVS)-these are vesicular structures of approximate 27 nm in diameter within neuronal processes-i.e. axonal terminal or dendrites. TVS are smaller and of higher electron density than synaptic vesicles. The significance of TVS remains unknown. 3. Dystrophic neurites. Dendrites or axonal preterminals and terminals filled with electron-dense bodies, including small autophagic vacuoles. 4. Apoptotic cell nuclei. 5. "Whorls", concentric arrays of membranes were visible. A significance of those structures is unknown.

Reflections on Cerebellar Neuropathology in Classical Scrapie

“…The spongiosis (micro- and macrovacuolization) observed in this pathology, a differential characteristic of the group of transmissible spongiform diseases, has not been well elaborated thus far, although it is of great importance in diagnosis [ 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 ]. In studies at the level of optical and electron microscopy, a large number of vacuoles with a size of 0.3 to 20 microns have been evidenced, outside the neurons in the neuropil.…”

“…The most frequently referenced are aggresomes, which are round electron-dense structures and not membrane-bound [ 81 ]; tubulovesicular structures (TVS, vesicular structures of higher electron density than synaptic vesicles, of approximately 27 nm in diameter within axonal terminal or dendrites) of unknown significance; electron-dense bodies; “whorls” or concentric arrays of membranes; debris of apoptotic cell nuclei, etc. [ 76 , 81 , 82 , 83 , 84 , 85 , 86 , 87 ]. It should also be noted that in normal sheep, many smooth endoplasmic reticulum formations are observed in the soma and dendrites of PCs (“spine apparatus”, hypolemmal cisterns), which can give rise to very extensive tubulovesicular formations of unknown significance, although they are not necessarily pathological.…”

“…The evolution of areas of high synapse concentration in scrapie has been reported in several experimental studies. In different neuronal types, especially in Purkinje neurons, various types of morphological alterations have been shown (as mentioned above), especially at the level of EM, and they have been interpreted in different ways over the years [ 76 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 ]. Some alterations (especially the so-called “tubulovesicular structures”) were primarily considered to be specific for prion diseases but were later “declassified” as pathognomonic markers of the disease [ 84 , 85 , 86 , 87 ].…”