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Expression of the chemokine receptor CXCR2 during remyelination and its influence on oligodendrocytes
M. Stangel, M. Lindner, C. Pitz, S. Heine, S. Maysami
In: 21st Congress of the European Committee for the Treatment and Research in Multiple Sclerosis; 28 Sep 2005-01 Oct 2005; http://www.ncbi.nlm.nih.gov/pubmed/16229091 . 10th Annual Meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis, Thessaloniki, Greece: ACTRIMS; 2005.
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Abstract
To understand the mechanisms of remyelination is one of the major challenges in multiple sclerosis research. By using a model of toxic demyelination, the cuprizone model, we investigated factors involved in the remyelination process. We found that the chemokine receptor CXCR2 is expressed on oligodendrocytes during remyelination and thus CXCR2 may play a role in the regulation of oligodendrocyte responses in vivo. C57BL/6 mice were fed a 0.3 % cuprizone diet for 6 weeks. After withdrawl of cuprizone animals stayed on normal chow for another 6 weeks. At different timepoints brains were removed and embedded in paraffin. Sections were stained immunhistochemically for CXCR2 and NG2 (a marker for oligodendrocyte precursors) in serial sections. Luxol-fast-blue (LFB-PAS) staining was used to quantify de- and remyelination. LFB-PAS staining revealed a nearly complete demyelination of the corpus callosum after 6 weeks of cuprizone treatment. Remyelination occurred spontaneously after withdrawl from the diet and myelin apeared normal after 6 weeks. CXCR2 positive oligodendrocyte precursor cells could be observed during the whole process of remyelination. In vitro experiments with oligodenrocyte progenitor cells (OPC) were performed to study the influence of the chemokine CXCL1 (ligand of CXCR2) on OPC regarding proliferation (BrdU incorporation), migration (boyden chemotaxis chamber) and differentiation (immuncytochemistry). OPC functions were influenced concentration dependent with an inhibition of migration that peaked at 1 ng/ml, while proliferation was increased at 0.5 ng/ml and differentiation augmented at 10 ng/ml.Our in vivo results suggest that the chemokine receptor CXCR2 is involved in the remyelination process. The in vivo results are underlined by the in vitro data demonstrating that the ligand CXCL1 is able to modulate the behaviour ofoligodendrocytes.
Keyword(s)
Chemokine; Cuprizone; Demyelination; Differentiation; Migration; Oligodendrocyte; Progenitor; Proliferation