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57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN)

German Society for Neuropathology and Neuroanatomy

12. - 15.09.2012, Erlangen

57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN)

The pro-apoptotic bcl-2 family member Puma but not Noxa is essential for cuprizone-induced oligodendroglial cell death

Meeting Abstract

  • presenting/speaker Karin Hagemeier - Neuropathology, University Hospital Münster, Münster, Germany
  • Alexander Lürbke - Neuropathology, University Hospital Münster, Münster, Germany
  • Stephanie Hucke - Neurology- Inflammatory Diseases and Neurooncology, University Hospital Münster, Münster, Germany
  • Stefanie Albrecht - Neuropathology, University Hospital Münster, Münster, Germany
  • Anna Preisner - Neuropathology, University Hospital Münster, Münster, Germany
  • Elena Klassen - Neuropathology, University Hospital Münster, Münster, Germany
  • Amke Hesse - Neuropathology, University Hospital Münster, Münster, Germany
  • Elke Hoffmann - Neuropathology, University Hospital Münster, Münster, Germany
  • Wolfgang Brück - Neuropathology, University Hospital Göttingen, Göttingen, Germany
  • Luisa Klotz - Neurology- Inflammatory Diseases and Neurooncology, University Hospital Münster, Münster, Germany
  • Tanja Kuhlmann - Neuropathology, University Hospital Münster, Münster, 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. Doc12dgnnPP2.2

DOI: 10.3205/12dgnn038, URN: urn:nbn:de:0183-12dgnn0388

Published: September 11, 2012

© 2012 Hagemeier et al.
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Outline

Text

Multiple sclerosis (MS) lesions are characterized by inflammation, demyelination and
oligodendroglial loss. The mechanisms leading to oligodendroglial cell death are still incompletely understood. Therefore, the aim of this study was the identification of the molecular pathways involved in oligodendroglial cell death. Using microarray analysis we identified the candidate genes Puma and Noxa as being upregulated during cuprizone induced demyelination in C57Bl/6J mice. Puma (p53 upregulated modulator of apoptosis) and Noxa (Latin for damage) are pro-apoptotic members of the BH3 (Bcl-2 homology 3)-only protein family. When feeding Puma deficient and wild type mice with 0.1% cuprizone in powdered chow, Puma deficient mice showed dramatically reduced numbers of apoptotic oligodendrocytes and activated microglia in the corpora callosa compared to wild type littermates. In contrast, Noxa deficient and wild type mice did not show a significant difference in cell death or microglial activation. In order to confirm these results as well as to validate that these effects originate from oligodendrocytes, oligodendrocyte precursor cells (OPCs) were cultured from Puma and Noxa deficient and wild type littermates using an immunopanning protocol. Puma deficient OPCs showed reduced cell death susceptibility under normal cell culture conditions as well as after staurosporine or nitric oxide induced cell death compared to wild type littermates. Additionally, a significant increase in myelin gene expression on mRNA level could be observed in Puma deficient oligodendrocytes compared to wild type cells. In contrast, Noxa deficient OPCs did not show a difference in cell viability or myelin gene expression. When examining microglia cells obtained from Puma deficient and wild type littermates that where stimulated with LPS/IFNγ, Puma deficient cells showed a slightly reduced inflammatory response on mRNA levels compared to wild type cells. Furthermore we analysed the expression of Puma in MS lesions and were able to detect Puma positive oligodendrocytes in normal appearing white matter (NAWM) as well as in MS lesions. In summary, our data demonstrate that Puma but not Noxa is essential for oligodendroglial cell death in cuprizone induced demyelination and might also play a role in oligodendroglial cell loss in MS.