Low Copper and High Manganese Levels in Prion Protein Plaques

Viruses

Christopher J. Johnson¹  P.U.P.A. Gilbert²  Mike Abrecht³  Katherine L. Baldwin⁵  Robin E. Russell¹  Joel A. Pedersen⁵  Judd M. Aiken⁴ 

[1] USGS National Wildlife Health Center, 6006 Schroeder Road, Madison, WI 53711, USA; E-Mails:;Department of Physics, University of Wisconsin-Madison, 1150 University Avenue, Madison, WI 53706, USA; E-Mails:;Centre for Prions and Protein Folding Diseases, AFNS, University of Alberta, Edmonton, Alberta, T6G 2M8, Canada; E-Mail:;Program in Cellular & Molecular Biology, University of Wisconsin-Madison, 425-G Henry Mall Madison, WI 53706, USA; E-Mail:

关键词: transmissible spongiform encephalopathy;    X-ray photoemission;    copper;    manganese;    prion;    brain;   

DOI  :  10.3390/v5020654

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.