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Bioluminescence Imaging to Detect Late Stage Infection of African Trypanosomiasis
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Measuring prions by bioluminescence imaging.

Gültekin Tamgüney1, Kevin P Francis, Kurt Giles

  • 1Institute for Neurodegenerative Diseases and Department of Neurology, University of California, San Francisco, CA 94143, USA.

Proceedings of the National Academy of Sciences of the United States of America
|August 27, 2009
PubMed
Summary
This summary is machine-generated.

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Bioluminescence imaging (BLI) detects prion disease in mice using GFAP. This method is faster and as sensitive as traditional methods for measuring prion infectivity in research.

Area of Science:

  • Neuroscience
  • Biochemistry
  • Infectious Diseases

Background:

  • Prion diseases are fatal neurodegenerative disorders.
  • Astrocytic gliosis, indicated by glial fibrillary acidic protein (GFAP) deposition, is a hallmark of prion disease.
  • GFAP's role suggests it could serve as a surrogate marker for prions.

Purpose of the Study:

  • To investigate if GFAP can be used as a surrogate marker for prion detection.
  • To evaluate bioluminescence imaging (BLI) as a noninvasive method for monitoring prion disease progression.
  • To determine if BLI can serve as a proxy bioassay for prion infectivity.

Main Methods:

  • Transgenic (Tg) mice (Tg(Gfap-luc)) expressing luciferase under the GFAP promoter were inoculated with prions.
  • Noninvasive weekly bioluminescence imaging (BLI) was used to monitor light emission from mouse brains.

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  • Endpoint titration studies were conducted to compare BLI sensitivity with traditional neurological assessments.
  • Main Results:

    • BLI detected increased light emission in the brains of Tg(Gfap-luc) mice around 55 days post-inoculation.
    • This detection occurred approximately 62 days before the onset of clinical neurological deficits.
    • BLI bioassays demonstrated equal or greater sensitivity compared to neurological dysfunction onset and were completed in half the time.

    Conclusions:

    • BLI is a suitable surrogate for measuring prion infectivity in Tg mouse models.
    • This noninvasive imaging technique can significantly accelerate prion disease research.
    • BLI may be applicable to studying other neurodegenerative diseases in transgenic mouse models.