Year: 2016
Type: article
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.
DOI: 10.1084/jem.20151000
Authors: Caihong Zhu, Uli S. Herrmann, Jeppe Falsig, Irina Abakumova, Mario Nuvolone, Petra Schwarz, Katrin Frauenknecht, Elisabeth J. Rushing, Adriano Aguzzi
Institution: University Hospital Zurich
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
Award: G7857579262
OpenAlex ID: W2406691442