Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-39975
Kranich, J; Krautler, N J; Falsig, J; Ballmer, B; Li, S; Hutter, G; Schwarz, P; Moos, R; Julius, C; Miele, G; Aguzzi, A (2010). Engulfment of cerebral apoptotic bodies controls the course of prion disease in a mouse strain-dependent manner. Journal of Experimental Medicine, 207(10):2271-2281.
Progressive accumulation of PrP(Sc), a hallmark of prion diseases, occurs when conversion of PrP(C) into PrP(Sc) is faster than PrP(Sc) clearance. Engulfment of apoptotic bodies by phagocytes is mediated by Mfge8 (milk fat globule epidermal growth factor 8). In this study, we show that brain Mfge8 is primarily produced by astrocytes. Mfge8 ablation induced accelerated prion disease and reduced clearance of cerebellar apoptotic bodies in vivo, as well as excessive PrP(Sc) accumulation and increased prion titers in prion-infected C57BL/6 × 129Sv mice and organotypic cerebellar slices derived therefrom. These phenotypes correlated with the presence of 129Sv genomic markers in hybrid mice and were not observed in inbred C57BL/6 Mfge8(-/-) mice, suggesting the existence of additional strain-specific genetic modifiers. Because Mfge8 receptors are expressed by microglia and depletion of microglia increases PrP(Sc) accumulation in organotypic cerebellar slices, we conclude that engulfment of apoptotic bodies by microglia may be an important pathway of prion clearance controlled by astrocyte-borne Mfge8.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology|
|DDC:||570 Life sciences; biology|
610 Medicine & health
|Deposited On:||19 Jan 2011 19:49|
|Last Modified:||28 Nov 2013 01:02|
|Publisher:||Rockefeller University Press|
|Additional Information:||© 2010 Kranich et al.|
|Free access at:||PubMed ID. An embargo period may apply.|
|Citations:||Web of Science®. Times Cited: 25|
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