Shown on lab hamsters; time to look at actual
wildlife and bovine brains, affected in real-world
settings, not laboratory induced. Getting closer.
Viruses. 2013 Feb 11;5(2):654-62. doi:
10.3390/v5020654.
Low copper and high manganese levels in prion
protein plaques.
Johnson CJ, Gilbert PU, Abrecht M, Baldwin KL,
Russell RE, Pedersen JA, Aiken JM, McKenzie D.
Source
USGS National Wildlife Health Center, 6006
Schroeder Road, Madison, WI 53711, USA.
debbie.mckenzie@ualberta.ca.
Abstract
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.
PMID: 23435237 [PubMed - in process]
wildlife and bovine brains, affected in real-world
settings, not laboratory induced. Getting closer.
Viruses. 2013 Feb 11;5(2):654-62. doi:
10.3390/v5020654.
Low copper and high manganese levels in prion
protein plaques.
Johnson CJ, Gilbert PU, Abrecht M, Baldwin KL,
Russell RE, Pedersen JA, Aiken JM, McKenzie D.
Source
USGS National Wildlife Health Center, 6006
Schroeder Road, Madison, WI 53711, USA.
debbie.mckenzie@ualberta.ca.
Abstract
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.
PMID: 23435237 [PubMed - in process]
Comment