NR AXLW

AU Falsig,J.; Heppner,F.L.; Julius,C.; Schwarz,P.; Aguzzi,A.

TI Microglia Depletion Increases Prion Replication in Organotypic Brain Slices

QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.177

IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf

PT Konferenz-Poster

AB Transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative diseases characterized by accumulation of PrPsc, an abnormal isoform of the cellular protein PrPc. Microglia is associated with PrPsc plaques in TSE brains, but their role in prion turnover is unknown. We have established a prion organotypic slice culture assay (POSCA) to investigate the contribution of microglia to prion replication in CNS tissue. Thirty-five days after contact with prions, cerebellar slices from wild-type mice had amplified disease-associated prion protein >105-fold, similarly to terminally sick mice. PrPsc accumulated predominantly in the molecular layer, similarly to infected mice. We then performed POSCA on slices from CD11b-HSV-TK transgenic mice from which microglia can be selectively removed. Microglia depletion led to a 15-fold increase in prion and PrPsc concentration and to increased susceptibility to infection. These results support a protective role for microglia against prion replication.

AD J. Falsig, F.L. Heppner, C. Julius, P. Schwarz, A. Aguzzi, Zürich University Hospital, Neuropathology, Switzerland

SP englisch

PO Schottland

EA pdf-Datei und Poster (Posterautoren: J. Falsig, C. Julius, I. Margalith, P. Schwarz, F. Heppner und A. Aguzzi; Postertitel: A versatile prion replication assay in organotypic brain slices)

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