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

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie

12. - 15.09.2012, Erlangen

Banner: 57. Jahrestagung der Deutschen Gesellschaft für Neuropathologie und Neuroanatomie

Alpha-synuclein expressing CG4 cell line: a possible in vitro model for multiple system atrophy

Meeting Abstract

  • presenting/speaker Benjamin Ettle - University Hospital Erlangen, Molecular Neurology, Erlangen, Germany; Friedrich-Alexander University Erlangen-Nuremberg, Master's program Molecular Medicine, Erlangen, Germany
  • Verena May - University hospital Erlangen, Molecular Neurology, Erlangen, Germany
  • Michael Wegner - Friedrich-Alexander University Erlangen-Nuremberg, Institute of Biochemistry, Erlangen, Germany
  • Jochen Klucken - University hospital Erlangen, Molecular Neurology, Erlangen, Germany
  • Jürgen Winkler - University hospital Erlangen, Molecular Neurology, Erlangen, Germany

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie. 57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN). Erlangen, 12.-15.09.2012. Düsseldorf: German Medical Science GMS Publishing House; 2012. Doc12dgnnPP4.21

doi: 10.3205/12dgnn098, urn:nbn:de:0183-12dgnn0984

Veröffentlicht: 11. September 2012

© 2012 Ettle et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen ( Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.



Multiple system atrophy (MSA) is a rare atypical Parkinson syndrome categorized as alpha-synucleinopathy. Common neuropathological characteristics of MSA are a profound and widespread neuronal loss in the striatum, cerebellum, brain stem, and cortex as well as myelin pallor, astrogliosis, microgliosis, and alpha-synuclein aggregation in oligodendrocytes and neurons. In oligodendrocytes of MSA patients, alpha-synuclein is observed within glial cytoplasmatic inclusions (GCIs). The origin as well as the development of these GCIs is still not well understood. To better delineate this process, we analyzed the ability of an oligodendroglial cell line (Central Glia 4; CG4) to take up extracellular alpha-synuclein. Indeed, we detected alpha-synuclein immunopositive inclusions in CG4 cells after 72 h exposure to recombinant human wild-type alpha-synuclein (20 µM). Furthermore, a human wild-type alpha-synuclein expressing CG4 cell line (CG4-WTS) was generated to assess the ability of oligodendrocytes to release alpha-synuclein. However, no alpha-synuclein was detected in supernatants of CG4-WTS cells. Previous neuropathological studies focusing on the transcriptional control of oligodendrogenesis in MSA patients and its preclinical models are rare. Thus, we analyzed the expression profiles of oligodendroglial transcription factors crucial for differentiation comparing CG4 with CG4-WTS cells. We observed that mRNA of hairy enhancer of split-5 (Hes5), an effector of Notch-signaling repressing oligodendrocytic differentiation, is significantly increased in CG4-WTS cells whereas levels of myelin regulatory factor (MRF)-mRNA, an important activator for myelin genes, was significantly reduced. This expression profile suggests that alpha-synuclein delays oligodendrocytic differentiation. Taken together, our results reveal new insights into alpha-synuclein associated pathology of oligodendrocytes in MSA.