title: A neuroprotective role for microglia in prion diseases.
abstract: Microglial activation is a hallmark of most neurodegenerative disorders, and is particularly conspicuous in prion diseases. However, the role of microglia, which function as both primary immune effector cells and professional phagocytes in the central nervous system, remains contentious in the context of neurodegeneration. Here, we evaluated the effect of microglial depletion/deficiency on prion pathogenesis. We found that ganciclovir-mediated microglial ablation on tga20/CD11b-thymidine kinase of Herpes simplex virus (HSVTK) cerebellar organotypic cultured slices markedly aggravated prion-induced neurotoxicity. A similar deterioration of disease was recapitulated in in vivo microglial depletion in prion-infected tga20/CD11b-HSVTK mice. Additionally, deficiency of microglia in interleukin 34 knockout (IL34(-/-)) mice again resulted in significantly augmented proteinase K-resistant prion protein deposition and accelerated prion disease progression. These results provide unambiguous evidence for a general protective role of microglia in prion pathogenesis.
authors.affiliation: Institute of Neuropathology, University Hospital Zurich, 8091 Zurich, Switzerland Adriano.Aguzzi@usz.ch Caihong.Zhu@usz.ch.
authors.forename: Caihong
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Institute of Neuropathology, University Hospital Zurich, 8091 Zurich, Switzerland.
authors.forename: Uli S
authors.initials: US
authors.lastname: Herrmann
authors.affiliation: Institute of Neuropathology, University Hospital Zurich, 8091 Zurich, Switzerland.
authors.forename: Jeppe
authors.initials: J
authors.lastname: Falsig
authors.affiliation: Institute of Neuropathology, University Hospital Zurich, 8091 Zurich, Switzerland.
authors.forename: Irina
authors.initials: I
authors.lastname: Abakumova
authors.affiliation: Institute of Neuropathology, University Hospital Zurich, 8091 Zurich, Switzerland.
authors.forename: Mario
authors.initials: M
authors.lastname: Nuvolone
authors.affiliation: Institute of Neuropathology, University Hospital Zurich, 8091 Zurich, Switzerland.
authors.forename: Petra
authors.initials: P
authors.lastname: Schwarz
authors.affiliation: Institute of Neuropathology, University Hospital Zurich, 8091 Zurich, Switzerland.
authors.forename: Katrin
authors.initials: K
authors.lastname: Frauenknecht
authors.affiliation: Institute of Neuropathology, University Hospital Zurich, 8091 Zurich, Switzerland.
authors.forename: Elisabeth J
authors.initials: EJ
authors.lastname: Rushing
authors.affiliation: Institute of Neuropathology, University Hospital Zurich, 8091 Zurich, Switzerland Adriano.Aguzzi@usz.ch Caihong.Zhu@usz.ch.
authors.forename: Adriano
authors.initials: A
authors.lastname: Aguzzi
mesh_terms: D000818:Animals; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism* / Q000473:pathology; D017096:Prion Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011328:Prions / Q000235:genetics / Q000378:metabolism*
chemical_list: D007378:Interleukins; D011328:Prions; C552364:interleukin-34, mouse