gms | German Medical Science

Joint-Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN) and the Scandinavian Neuropathological Society (SNS)

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie

22.09.-24.09.2016, Hamburg

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Neuroinvasion of α-synuclein prionoids after intraperitoneal injection

Meeting Abstract

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  • Sara Breid - German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
  • Maria Eugenia Bernis - German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
  • Julius Tachu Babila - German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
  • Maria Carmen Garza - University of Alberta, Centre for Prions and Protein Folding Diseases & Department of Biochemistry, Edmonton, Canada
  • Holger Wille - University of Alberta, Centre for Prions and Protein Folding Diseases & Department of Biochemistry, Edmonton, Canada
  • presenting/speaker Gültekin Tamgüney - German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie. Scandinavian Neuropathological Society. Joint-Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN) and the Scandinavian Neuropathological Society (SNS). Hamburg, 22.-24.09.2016. Düsseldorf: German Medical Science GMS Publishing House; 2016. Doc16dgnnPR4

doi: 10.3205/16dgnn07, urn:nbn:de:0183-16dgnn077

Veröffentlicht: 14. September 2016

© 2016 Breid 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: α-Synuclein is a soluble, cellular protein that in a number of neurodegenerative diseases forms pathologic protein deposits such as glial cytoplasmic inclusions in oligodendrocytes in multiple system atrophy or Lewy bodies in Parkinson’s disease. Misfolded α-synuclein has been reported to show a prion-like spread after intracerebral injection into transgenic and wild type mice.

Objectives: Here we investigated the potential of misfolded α-synuclein to induce disease after intraperitoneal challenge.

Materials & Methods: We used bigenic Tg (M83:Gfap-luc) mice that hemizygously express the A53T-mutant of human α-synuclein and firefly luciferase and when uninoculated remain healthy for over 600 d. These mice were injected with recombinant human wild type α-synuclein fibrils or phosphate-buffered saline as control into the peritoneal cavity.

Results: Intraperitoneal injection with α-synuclein fibrils but not phosphate-buffered saline led to neurologic disease with paralysis and kyphosis and α-synuclein pathology in the central nervous system of four out of five mice with a median incubation time of 229 ± 17 d. Diseased mice accumulated aggregates of sarkosyl-insoluble and phosphorylated α-synuclein in brain and spinal cord, which colocalized with ubiquitin and p62 and were accompanied by gliosis.

Conclusion: Our findings show that similar to prions, α-synuclein prionoids can neuroinvade the central nervous system after a single intraperitoneal injection and cause neuropathology and disease.