Co-expression of PDGF alpha receptor and NG2 by oligodendrocyte precursors in human CNS and multiple sclerosis lesions

Following inflammatory demyelination in multiple sclerosis (MS), partial remyelination occurs. Studies in rodents have indicated that oligodendrocyte precursor cells (OPCs) are responsible for this remyelination. Rodent OPCs are identified in situ with antibodies against platelet-derived growth factor alpha receptor (PDGFalphaR) and NG2 chondroitin sulfate proteoglycan. In human CNS tissue, studies of NG2 and PDGFalphaR expression are limited and controversy exists as to whether these molecules are specific OPC markers. This study has investigated whether PDGFalphaR and NG2 are co-expressed on OPCs in human CNS, and whether OPCs are associated with remyelination in MS. MS brain tissue was examined for PDGFalphaR and NG2 immunoreactivity and for expression of NG2 mRNA by in situ hybridisation. Putative OPCs, expressing both NG2 and PDGFalphaR, were present within normal-appearing white matter and within areas of active demyelination in MS, but not in chronic silent lesions. They were also seen in association with remyelination in MS tissue and with developmental myelination in human spinal cord. NG2+ cells that did not express PDGFalphaR were also detected. Given their lack of reactivity with microglial or astrocyte markers, these NG2+/PDGFalphaR- cells probably represented more mature OPCs that had lost PDGFalphaR expression. The distribution of OPCs observed in this study strongly suggests these cells are potential sources of remyelinating oligodendrocytes in active lesions in MS.