Related Experiment Video
Updated: Jul 19, 2026
Rapid and Refined CD11b Magnetic Isolation of Primary Microglia with Enhanced Purity and Versatility
Published on: April 13, 2017
Early and rapid engraftment of bone marrow-derived microglia in scrapie
Josef Priller1, Marco Prinz, Mathias Heikenwalder
1Institute of Neuropathology, Department of Pathology, University of Zurich, 8091 Zurich, Switzerland. josef.priller@charite.de
Abstract:
Prion neuroinvasion is accompanied by maximal activation of microglia, the significance of which for pathogenesis is unknown. Here, we used bone marrow (BM) cells expressing GFP (green fluorescent protein) to study the turnover of microglia in mouse scrapie. We found that >or=50% of all brain microglia were replaced by BM-derived cells before clinical disease onset. In terminally sick mice, microglia density increased threefold to fourfold. Hence BM-derived microglia rapidly and efficaciously colonize the brain in scrapie. Whereas reconstitution of wild-type mice with prion protein-deficient (Prnp(o/o)) BM did not alter scrapie pathogenesis, Prnp(o/o) mice transplanted with wild-type BM cells were resistant to peripherally administered prions despite high levels of infectivity in the spleen. Cerebellar homogenates from prion-inoculated Prnp(o/o) mice reconstituted with >10% of wild-type microglia failed to infect transgenic mice overexpressing the cellular prion protein. Hence, in contrast to previous reports, microglia are not competent for efficient prion transport and replication in vivo.
Insights
Bone marrow-derived cells rapidly replace brain microglia during scrapie infection in mice. These microglia are not competent for efficient prion transport or replication, challenging previous findings.
Area of Science:
- Neuroscience
- Immunology
- Infectious Diseases
Background:
- Microglia, the brain's immune cells, are activated during prion diseases like scrapie.
- The role of microglia in prion pathogenesis and neuroinvasion remains unclear.
Purpose of the Study:
- To investigate microglia turnover and function in prion neuroinvasion using mouse scrapie models.
- To determine if microglia are essential for prion transport and replication in vivo.
Main Methods:
- Utilized green fluorescent protein (GFP)-expressing bone marrow (BM) cells to track microglia replacement in mice with scrapie.
- Employed bone marrow transplantation techniques using wild-type and prion protein-deficient (Prnp(o/o)) mice.
Main Results:
- Over 50% of brain microglia were replaced by BM-derived cells before clinical scrapie onset.
- Prnp(o/o) mice transplanted with wild-type BM cells showed resistance to peripheral prions.
- Brain homogenates from prion-inoculated Prnp(o/o) mice with limited wild-type microglia failed to infect other mice.
Conclusions:
- Bone marrow-derived microglia efficiently colonize the brain during scrapie.
- Microglia are not competent for efficient prion transport and replication in vivo, contradicting prior studies.
