Myelinosome formation represents an early stage of oligodendrocyte damage in multiple sclerosis and its animal model

نویسندگان

  • Elisa Romanelli
  • Doron Merkler
  • Aleksandra Mezydlo
  • Marie-Theres Weil
  • Martin S. Weber
  • Ivana Nikić
  • Stephanie Potz
  • Edgar Meinl
  • Florian E. H. Matznick
  • Mario Kreutzfeldt
  • Alexander Ghanem
  • Karl-Klaus Conzelmann
  • Imke Metz
  • Wolfgang Brück
  • Matthew Routh
  • Mikael Simons
  • Derron Bishop
  • Thomas Misgeld
  • Martin Kerschensteiner
چکیده

Oligodendrocyte damage is a central event in the pathogenesis of the common neuroinflammatory condition, multiple sclerosis (MS). Where and how oligodendrocyte damage is initiated in MS is not completely understood. Here, we use a combination of light and electron microscopy techniques to provide a dynamic and highly resolved view of oligodendrocyte damage in neuroinflammatory lesions. We show that both in MS and in its animal model structural damage is initiated at the myelin sheaths and only later spreads to the oligodendrocyte cell body. Early myelin damage itself is characterized by the formation of local myelin out-foldings-'myelinosomes'-, which are surrounded by phagocyte processes and promoted in their formation by anti-myelin antibodies and complement. The presence of myelinosomes in actively demyelinating MS lesions suggests that oligodendrocyte damage follows a similar pattern in the human disease, where targeting demyelination by therapeutic interventions remains a major open challenge.

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عنوان ژورنال:

دوره 7  شماره 

صفحات  -

تاریخ انتشار 2016