gms | German Medical Science

60. Jahrestagung der Deutschen Gesellschaft für Neuropathologie und Neuroanatomie (DGNN)

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie

26. - 28.08.2015, Berlin

Activation of resident brain microglia by viral infection leads to transient clearance of infectious prions from the brain

Meeting Abstract

  • corresponding author presenting/speaker Susanne Krasemann - University Medical Center Hamburg-Eppendorf UKE, Institute for Neuropathology, Hamburg, Germany
  • Katharina Schröck - University Medical Center Hamburg-Eppendorf UKE, Institute for Neuropathology, Hamburg, Germany
  • Zain Fanek - Brigham and Womens Hospital, Harvard Medical School, Boston, United States
  • Oleg Butovsky - Brigham and Womens Hospital, Harvard Medical School, Boston, United States
  • Markus Glatzel - University Medical Center Hamburg-Eppendorf UKE, Institute for Neuropathology, Hamburg, Germany

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie. 60th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN). Berlin, 26.-28.08.2015. Düsseldorf: German Medical Science GMS Publishing House; 2015. Doc15dgnnND6

doi: 10.3205/15dgnn06, urn:nbn:de:0183-15dgnn067

Veröffentlicht: 25. August 2015

© 2015 Krasemann et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.


Gliederung

Text

Introduction: Prion diseases are transmissible, fatal disorders, where the conversion of the cellular prion protein (PrPC) into a misfolded variant (PrPSc) leads to neurodegeneration. The spreading of the misfolded isoform to and within the brain is an essential step in the establishment and spreading of the disease.

Objectives: In this study, we wanted to assess the interplay of prion and retrovirus infections on the spreading of misfolded prion proteins and disease outcome.

Materials and methods: We used an established prion disease mouse model (RML 5.0) with defined incubation times and brain pathology. For retrovirus infection, we choose the molecular clone Mov3 of the murine retrovirus MoMuLV, since we could show that intraperitoneal injection led to persistent retrovirus infection without overt disease with our inoculation scheme. PrPSc amount was determined by Western blot and immunohistochemistry, whereas the titers of infectious prions in brain and spleen tissue were assessed by bioassay.

Results: In the early phases of the prion disease, an additional virus infection lead to a complete clearance of infectious prion species from the brain. This was accompanied by a transient increase of microglia numbers but no recruitment of monocytes from the periphery. The molecular profile of the retrovirus activated microglia was assessed via nCounter Nanostring analysis and showed upregulation of genes involved in protein degradation. However, transient microglia activation in the early disease phase did not lead to changes in prion disease outcome.

Conclusion: In our study, we could demonstrate transient clearance of infectious prion proteins by microglia activated via retrovirus infection, but this did not lead to differences in disease outcome. However, studies like this might help to characterize and understand microglia function and eventually help to manipulate microglia to reactivate their function in neurodegenerative diseases.