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Ubiquitin conjugate immunoreactivity in the brains of scrapie infected mice
J Lowe1, H McDermott, N Kenward
1Department of Pathology, University of Nottingham Medical School, Queens Medical Centre, U.K.
Abstract:
Sections of brain from normal mice or clinically-ill mice infected with either the 87V or the ME7 strains of sheep scrapie were immunostained to show the localization of ubiquitin-protein conjugates or a specific marker of disease, the scrapie-associated fibril protein (PrP). In both scrapie models immunoreactive ubiquitin-protein conjugates were seen in thread-like structures found throughout the neuropil, in inclusion bodies within vacuolated neurones, and in areas surrounding anti-PrP positive amyloid plaques. The PrP protein was visualized in diffuse deposits in highly vacuolated parts of the scrapie-affected brain, and focally in amyloid plaques, microglia and neuronal processes. The ubiquitin-protein conjugate staining of scrapie amyloid plaques is very similar to that seen in the plaques of Alzheimer's disease. The ubiquitinated intraneuronal inclusion bodies seen in scrapie resemble the granulovacuolar lesions also seen in Alzheimer's disease, but appear much larger and possibly correspond to material in giant autophagic vacuoles. We suggest that these inclusions may be the result of ubiquitinated abnormal proteins being directed to the lysosomal system, and that scrapie and Alzheimer's disease share at least some common processes of neurodegeneration.
Insights
Scrapie infection in mice shows abnormal protein buildup, similar to Alzheimer's disease pathology. This suggests shared cellular mechanisms in neurodegeneration for both prion and Alzheimer's diseases.
Area of Science:
- Neuroscience
- Pathology
- Biochemistry
Background:
- Scrapie is a prion disease affecting sheep, characterized by neurodegeneration.
- Alzheimer's disease is a neurodegenerative disorder associated with amyloid plaques and neurofibrillary tangles.
Purpose of the Study:
- To investigate the localization of ubiquitin-protein conjugates and scrapie-associated fibril protein (PrP) in mouse models of scrapie.
- To compare the neuropathological features of scrapie with those of Alzheimer's disease.
Main Methods:
- Immunohistochemistry was used to detect ubiquitin-protein conjugates and PrP in brain sections from normal and scrapie-infected mice (strains 87V and ME7).
Main Results:
- Ubiquitin-protein conjugates were found in neuropil, neuronal inclusion bodies, and around amyloid plaques in scrapie-affected brains.
- PrP was detected in diffuse deposits, amyloid plaques, microglia, and neuronal processes.
- Scrapie amyloid plaques showed ubiquitin staining similar to Alzheimer's disease plaques.
- Intraneuronal ubiquitin inclusions in scrapie resembled granulovacuolar lesions in Alzheimer's disease but were larger.
Conclusions:
- Scrapie and Alzheimer's disease share common neuropathological features, including ubiquitinated protein aggregates.
- These findings suggest that the lysosomal system may be involved in the clearance of ubiquitinated abnormal proteins in both diseases.
- Shared cellular mechanisms of neurodegeneration may exist between prion diseases like scrapie and Alzheimer's disease.