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Serological evidence for an inflammatory response in murine scrapie
1Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana 59840, USA. jcoe@niaid.nih.gov
Abstract:
Transmissible spongiform encephalopathies (TSEs) are initiated by a novel kind of agent that produces characteristic degenerative changes in the brain without a detectable systemic inflammatory response or serological changes. A murine scrapie model was evaluated for changes in plasma concentration of serum amyloid P component (SAP), a protein that is up-regulated in infected and/or injured mice during the acute phase response (APR). C57BL10 and IRW mice inoculated with scrapie brain developed clinical scrapie 125-150 days later. At this time, concentration of plasma SAP increased in most of them. The SAP level increased > or =3-fold in >80% of the scrapie-affected C57BL10 mice and IRW male mice. A similar increase was found in <3% of respective nonscrapie control mice. The up-regulation of mouse SAP during clinical scrapie provides evidence for the activation of a systemic APR in TSE, a serological change that may be clinically useful.
Insights
Transmissible spongiform encephalopathies (TSEs) activate a systemic acute phase response (APR). Researchers observed increased serum amyloid P component (SAP) levels in mice with clinical scrapie, indicating a potential diagnostic marker.
Area of Science:
- Neuroscience
- Immunology
- Veterinary Medicine
Background:
- Transmissible spongiform encephalopathies (TSEs) cause brain degeneration without clear inflammation or serological changes.
- Serum amyloid P component (SAP) is a protein known to increase during the acute phase response (APR) in mice with infections or injuries.
Purpose of the Study:
- To investigate changes in plasma SAP concentration in a murine scrapie model.
- To determine if SAP up-regulation indicates a systemic APR in TSEs.
Main Methods:
- C57BL10 and IRW mice were inoculated with scrapie brain.
- Plasma SAP concentration was measured in mice that developed clinical scrapie and in control mice.
- SAP levels were quantified at the onset of clinical symptoms.
Main Results:
- Mice developed clinical scrapie 125-150 days post-inoculation.
- Plasma SAP concentration increased significantly (≥3-fold) in over 80% of scrapie-affected mice.
- Similar SAP increases were observed in less than 3% of control mice.
Conclusions:
- The up-regulation of SAP during clinical scrapie demonstrates a systemic APR in TSEs.
- Increased SAP levels represent a detectable serological change in TSEs.
- SAP may serve as a clinically useful marker for TSE diagnosis.
