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Tubulofilaments in negatively stained scrapie-infected brains: relationship to scrapie-associated fibrils

H K Narang1, D M Asher, D C Gajdusek

  • 1Laboratory of Central Nervous System Studies, National Institute of Neurological Diseases and Stroke, Bethesda, MD 20892.

Proceedings of the National Academy of Sciences of the United States of America
|November 1, 1987
PubMed

Insights

Researchers developed a simple method to visualize scrapie-associated fibrils (SAF) in infected brain tissue using electron microscopy. These fibrils appear to be internal components of larger structures disrupted by detergents.

Area of Science:

  • Neuroscience
  • Microbiology
  • Biochemistry

Background:

  • Scrapie and Creutzfeldt-Jakob disease are transmissible spongiform encephalopathies.
  • The exact structure and origin of disease-associated fibrils remain unclear.
  • Previous studies suggested scrapie-associated fibrils (SAF) are involved in disease pathogenesis.

Purpose of the Study:

  • To develop a simple method for visualizing scrapie-associated fibrils (SAF) in infected brain tissue.
  • To characterize the morphology of abnormal structures in scrapie-infected brains.
  • To investigate the relationship between tubulofilamentous structures and SAF.

Main Methods:

  • Negative-stain transmission electron microscopy of infected hamster and mouse brain tissue.
  • Treatment with sodium dodecyl sulfate (SDS) to induce fragmentation of structures.
  • Immunogold labeling to identify scrapie-associated fibrils (SAF).

Main Results:

  • Large masses of tubulofilamentous structures with irregular surfaces were observed in scrapie-infected hamster brains.
  • Similar, but less abundant, tubulofilaments were found in Creutzfeldt-Jakob disease-infected mouse brains.
  • SDS treatment revealed thinner fibrillary structures resembling SAF within the larger tubulofilaments, which were confirmed by immunogold labeling.

Conclusions:

  • Scrapie-associated fibrils (SAF) may exist as internal components of larger, detergent-disrupted structures in infected brain tissue.
  • The observed tubulofilamentous structures are distinct from normal microtubules.
  • These findings suggest SAF are not artifacts of extraction but integral disease-related structures.

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