gms | German Medical Science

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

The importance of oligodendrocytes for multiple sclerosis lesion formation

Meeting Abstract

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  • presenting/speaker Markus Kipp - RWTH Aachen University, Neuroanatomy, Aachen, Germany
  • Katharina Berger - RWTH Aachen University, Neuroanatomy, Aachen, Germany
  • Cordian Beyer - RWTH Aachen University, Neuroanatomy, Aachen, 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. Doc12dgnnPP2.4

DOI: 10.3205/12dgnn040, URN: urn:nbn:de:0183-12dgnn0401

Veröffentlicht: 11. September 2012

© 2012 Kipp et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

There is a growing body of evidence that focal microglia activation within the so called "normal appearing white matter" of multiple sclerosis (MS) patients precedes inflammatory demyelinating events. Recent reports suggest that oligodendrocytes might be involved in microglia activation. The aim of this study was to analyze the contribution of oligodendrocyte stress for microglia activation/attraction.

We used the toxic demyelination model cuprizone to study the association between oligodendrocyte stress and microglia cell activation. The expression of various chemokines in the isolated corpus callosum was analyzed by gene array studies and rt-PCR. The chemokine transcription pattern was related to oligodendrocyte stress and microglia activation on the histological and ultrastructural level. The cellular source of chemokines was addressed by in situ hybridization and subsequent immunohistochemical studies. CCL2, CCL3 and CXCL10-deficient animals were included, to study the relevance of these chemokines for early microglia activation. Various in vitro experiments were performed to study the direct relevance of oligodendrocyte stress for microglia activation and attraction.

We were able to show that short-term cuprizone feeding leads to oligodendrocyte stress and apoptosis with concomitant microgliosis. Gene expression studies revealed that the expression of distinct chemokines is induced early after initiation of cuprizone treatment, predominantly Cxcl10. Loss-of-function studies showed that CXCL10, but not CCL2 or CCL3 plays a role in early microgliosis. In situ hybridization showed that stressed oligodendrocytes express Cxcl10 mRNA and in vitro experiments suggest that oligodendrocyte-derived CXCL10 attracts microglia cells. Furthermore oligodendrocyte-derived CXCL10 induces a proinflammatory phenotype (M1) in cultured microglia.

Our results suggest that oligodendrocytes actively participate in the initiation of neuroinflammatory processes.