title: Early and rapid engraftment of bone marrow-derived microglia in scrapie.
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.
authors.affiliation: Institute of Neuropathology, Department of Pathology, University of Zurich, 8091 Zurich, Switzerland. josef.priller@charite.de
authors.forename: Josef
authors.initials: J
authors.lastname: Priller
authors.forename: Marco
authors.initials: M
authors.lastname: Prinz
authors.forename: Mathias
authors.initials: M
authors.lastname: Heikenwalder
authors.forename: Nicolas
authors.initials: N
authors.lastname: Zeller
authors.forename: Petra
authors.initials: P
authors.lastname: Schwarz
authors.forename: Frank L
authors.initials: FL
authors.lastname: Heppner
authors.forename: Adriano
authors.initials: A
authors.lastname: Aguzzi
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western / Q000379:methods; D001854:Bone Marrow Cells / Q000502:physiology*; D016026:Bone Marrow Transplantation; D002452:Cell Count / Q000379:methods; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry / Q000379:methods; D015870:Gene Expression / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000096:biosynthesis; D007150:Immunohistochemistry / Q000379:methods; D007239:Infections; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000502:physiology*; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics; D012313:RNA / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012608:Scrapie / Q000473:pathology* / Q000601:surgery
chemical_list: D016207:Cytokines; D000072002:Prion Proteins; D011328:Prions; C512657:Prnp protein, mouse; D049452:Green Fluorescent Proteins; D012313:RNA