Oligodendroglial markers in the cuprizone model of CNS de- and remyelination

Abstract

y. Oligodendrocytes are the myelinating cells of the central nervous system. Since many studies of demyelinating diseases focus their research on this cell type, there is growing interest for obtaining reliable markers that can specifically recognize oligodendroglia. Established markers are the myelin-associated neurite outgrowth inhibitor (NogoA), the transcription factor Olig2, and the antibody CC-1, the latter being directed against the protein adenomatous polyposis coli (APC). Unfortunately, it has been discussed whether APC and Olig2 could recognize astrocytes under pathological conditions as well. Hence, we performed immunohistochemical studies using the oligodendroglial markers NogoA, APC, and Olig2 in a murine model of cuprizone induced demyelination. We have found that APC colocalizes with NogoA and does not co-localize with the astrocytic marker GFAP. Olig2 shows co-localization with APC but there is also a small population of Olig2/GFAP double positive cells. Some Olig2/GFAP double positive cells are found in the corpus callosum in a narrow time window in which oligodendrocyte precursor cells proliferate in this model. In other brain regions including the cerebral cortex and hippocampus and in all regions in untreated control mice double positive Olig2/GFAP cells do not occur. In conclusion, our results underline that APC and NogoA are reliable markers for detection of mature oligodendrocytes. Olig2 is a suitable marker to stain cells of oligodendroglial origin but could be combined with GFAP to exclude the GFAP positive population of cells from the quantification of oligodendroglia.