Author Of 1 Presentation
PS14.05 - Remyelinating satellite oligodendrocytes provide a rescue strategy to protect neurons after cortical demyelination in multiple sclerosis
Abstract
Background
Remyelination is observed in the white and grey matter of patients with multiple sclerosis (MS). However, whether remyelinating oligodendrocytes arise from newly formed oligodendrocyte progenitor cells (OPCs) or from preexisting OPCs generated during development is not known.
Objectives
The aim of the study is to investigate the origin of remyelinating oligodendrocytes in MS. Therefore, we intensively studied oligodendrocytes, oligodendrocyte-proliferation and differentiation in MS and demyelinating models of MS.
Methods
We performed immunohistochemistry in white and grey matter lesions of patients with early MS obtained at biopsy and late cortical lesions of patients with progressive MS obtained at autopsy. In comparison, we analyzed experimental models of MS, targeting the cortex or the white matter.
Results
In experimental demyelination as well as MS we found very little proliferation of oligodendrocytes and only single mature oligodendrocytes with BrdU incorporation indicating that newly formed oligodendrocytes did not participate in remyelination. Actively remyelinating, breast carcinoma amplified sequence 1 (BCAS1)-positive oligodendrocytes were to identify active remyelination and find that BCAS1 positive myelinating oligodendrocytes were generated immediately after experimental lesion induction and in early active MS lesions. In MS, the total number of oligodendrocytes in the cerebral cortex of early active MS lesions remained unchanged, but decreased with disease duration. This was associated with increased numbers of TPPP/p25 mature oligodendrocytes, suggesting oligodendrocyte differentiation. Furthermore, we identified that a fraction of BCAS1 positive oligodendrocytes in the cerebral cortex are perineuronal satellite cells. These cells obtain a myelinating morphology and express MAG after toxic demyelination and in early MS indicating that these cells participate in remyelination. In progressive MS and at late remyelination time-points in animal models we observed increased numbers of TPPP/p25 positive satellite oligodendrocytes.
Conclusions
Our data show that remyelination is predominantly performed by preexisting oligodendrocytes and is most efficient immediately after demyelination. Furthermore, we were able to demonstrate for the first time that BCAS1 positive perineuronal satellite cells in the cerebral cortex serve as a pool to generate remyelinating oligodendrocytes after experimental demyelination and in MS.