Low Copper and High Manganese Levels in Prion Protein Plaques
| Autor: | Joel A. Pedersen, Pupa U. P. A. Gilbert, Mike Abrecht, Katherine L. Baldwin, Robin E. Russell, Christopher J. Johnson, Judd M. Aiken, Debbie McKenzie |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
In situ
Prions animal diseases brain Central nervous system lcsh:QR1-502 chemistry.chemical_element Hamster Manganese Biology lcsh:Microbiology Prion Diseases prion 03 medical and health sciences 0302 clinical medicine Virology Cricetinae medicine Animals Prion protein transmissible spongiform encephalopathy 030304 developmental biology 0303 health sciences Communication Neurodegeneration medicine.disease Copper nervous system diseases Infectious Diseases medicine.anatomical_structure chemistry Biochemistry copper Brainstem X-ray photoemission 030217 neurology & neurosurgery |
| Zdroj: | Viruses Viruses, Vol 5, Iss 2, Pp 654-662 (2013) |
| ISSN: | 1999-4915 |
| Popis: | Accumulation of aggregates rich in an abnormally folded form of the prion protein characterize the neurodegeneration caused by transmissible spongiform encephalopathies (TSEs). The molecular triggers of plaque formation and neurodegeneration remain unknown, but analyses of TSE-infected brain homogenates and preparations enriched for abnormal prion protein suggest that reduced levels of copper and increased levels of manganese are associated with disease. The objectives of this study were to: (1) assess copper and manganese levels in healthy and TSE-infected Syrian hamster brain homogenates; (2) determine if the distribution of these metals can be mapped in TSE-infected brain tissue using X-ray photoelectron emission microscopy (X-PEEM) with synchrotron radiation; and (3) use X-PEEM to assess the relative amounts of copper and manganese in prion plaques in situ. In agreement with studies of other TSEs and species, we found reduced brain levels of copper and increased levels of manganese associated with disease in our hamster model. We also found that the in situ levels of these metals in brainstem were sufficient to image by X-PEEM. Using immunolabeled prion plaques in directly adjacent tissue sections to identify regions to image by X-PEEM, we found a statistically significant relationship of copper-manganese dysregulation in prion plaques: copper was depleted whereas manganese was enriched. These data provide evidence for prion plaques altering local transition metal distribution in the TSE-infected central nervous system. |
| Databáze: | OpenAIRE |
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