Subventricular zone-derived neural stem cells and oligodendrogenesis

SILVESTROFF L., FRANCO P.G., SOTO E.F. AND PASQUINI J.M.

San Antonio, Texas, E.E.U.U.

Congreso; American Society for Neurochemistry 39th Annual Meeting; 2008

American Society for Neurochemistry

In previous studies we have found that in the subventricular zone (SVZ) of adult Wistar rats undergoing cuprizone-induced demyelination there was an expansion of a cell population showing an enhanced expression of the stem cell marker Nestin. These changes triggered by demyelination were reverted upon T3 administration, indicating that thyroid hormones (TH) could regulate the emergence of remyelinating oligodendrocytes (OLG) from the pool of proliferating cells. Our interest was to study the SVZ response to demyelination and the characteristics and dynamics of this cell population in vitro. The SVZ was surgically removed from the brains of normal adult rats and mechanically dissociated to a single cell suspension in GDMi-B27 supplemented culture medium with freshly added FCS, bFGF and EGF. Cultured explants in mitogen-containing media showed the presence of dividing and migrating cells. These cells expressed high levels of Nestin and glial acidic fibrilary protein (GFAP), indicating that they were neural stem cells (NSC) or neural progenitor cells (NPC). After mitogen removal from the culture media, cell morphology changed drastically and cells resembled that of astrocytes and/or of mature oligodendrocytes. Nestin expression was down regulated while oligodendrocyte markers such as myelin basic protein (MBP) and O4 showed strong immunoreactivity. Some cells expressed the neuron marker neuro-filament 200 (NF200) while other cells with astrocyte morphology expressed GFAP. These SVZ explants were used to study the effects of molecules that induce OLG differentiation such as transferrin or TH alone or in combination with proliferating and chemoatractant molecules or growth factors.