The presence of demyelinated plaques in the central nervous system is the hallmark of multiple sclerosis (MS). Some plaques remyelinate but others do not, leaving permanent damage. The reasons for this failure of repair are many, but one possible reason is the lack of migration of oligodendrocyte precursor cells to the lesion. The guidance molecules Semaphorin 3A and 3F, already known to direct oligodendroglial migration in development, may also be active in controlling oligodendrocyte precursor cell migration in MS, and hence may determine the ability of plaques to remyelinate. Here, in MS tissue and an experimental model of demyelination, we demonstrate a local source of these molecules around active demyelinating lesions, but not chronic plaques. We also provide evidence for their up-regulation at a distance from the lesion, in the neuronal cell bodies corresponding to the demyelinated axons. We propose that both of these mechanisms influence remyelination.
The subependymal zone (SEZ) of the lateral ventricles of the adult mouse brain hosts neurogenesis from a neural stem cell population with the morphology of astrocytes (termed type-B cells). Tenascin-C is a large extracellular matrix glycoprotein present in the SEZ that has been shown to regulate the development of embryonic neural stem cells and the proliferation and migration of early postnatal neural precursors. Here we show that tenascin-C is produced by type-B cells and forms a layer between SEZ and the adjacent striatum. Tenascin-C deficiency resulted in minor structural differences in and around the SEZ. However, the numbers of neural stem cells and their progeny remained unaffected, as did their regeneration after depletion of mitotic cells using the antimitotic drug cytosine--Darabinofuranoside. Our results reveal a remarkable ability of the adult neural stem cell niche to retain proper function even after the removal of major extracellular matrix molecules.
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