NR AVNY
AU Priller,J.; Prinz,M.; Heikenwalder,M.; Zeller,N.; Schwarz,P.; Heppner,F.L.; Aguzzi,A.
TI Early and rapid engraftment of bone marrow-derived microglia in scrapie
QU Journal of Neuroscience 2006 Nov 8; 26(45): 11753-62
PT comparative study; journal article; research support, n.i.h., extramural; research support, non-u.s. gov't
AB 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.
MH Animals; Animals, Newborn; Blotting, Western/methods; Bone Marrow Cells/*physiology; *Bone Marrow Transplantation; Cell Count/methods; Cells, Cultured; Cytokines/genetics/metabolism; Flow Cytometry/methods; Gene Expression/physiology; Green Fluorescent Proteins/biosynthesis; Immunohistochemistry/methods; Infection; Mice; Mice, Inbred C57BL; Mice, Knockout; Microglia/*physiology; Prions/genetics; RNA/biosynthesis; Reverse Transcriptase Polymerase Chain Reaction/methods; Scrapie/*pathology/surgery
AD Institute of Neuropathology, Department of Pathology, University of Zürich, 8091 Zürich, Switzerland. josef.priller@charite.de
SP englisch
PO USA