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Journal Article
Research Support, Non-U.S. Gov't
Neuronal autophagy and aggresomes constitute a consistent part of neurodegeneration in experimental scrapie.
We describe here a variety of autophagous forms encountered in the terminal stages of two models of scrapie in hamsters. We also show that the number of autophagic vacuoles increased through the incubation period in the 263K strain scrapie model. In addition, we demonstrated for the first time the presence of aggresomes in the neuronal cytoplasm in scrapie-affected hamster brains. We observed neuronal autophagic vacuoles in different stages of formation in the same specimens. However, this description is based on the subjective grading of the severity of changes, which may or may not equate to the stage of development. First, a part of the neuronal cytoplasm was sequestered by membranes (phagophores) and that part of the cytoplasm confined by membranes often exhibited increased electron density. The intracytoplasmic membranes multiplied in a labyrinth-like manner. The area taken up by autophagic vacuoles expanded and eventually a large proportion of the cytoplasm was transformed into an agglomeration mass of autophagic vacuoles. Occasionally a large but single autophagic vacuole was visible. Autophagic vacuoles developed not only in the neuronal perikarya but also in neuronal processes, eventually replacing the whole cross-section of affected neurites.Generally,there were few qualitative differences between these two models but hamsters inoculated with the 263K strain had more severe changes. In a few specimens there were round electron-dense structures that we identified as aggresomes. Aggresomes are not membrane-bound and were found in the cytoplasm of a few neurons.
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