CONICET | Buscador de Institutos y Recursos Humanos

Neural progenitorcells (NPCs) from the subventricular zone (SVZ) are the source of new neurons,astrocytes and oligodendrocytes in the adult brain. Both Notch and TGF-β signalingpathways have been shown to act synergistically in co-cultures of mesenchymalstromal cells and NPCs, inducing NPC differentiation into astrocytes and oligodendrocytes.Taking into account the possible participation of NPC in the responsemechanisms upon demyelination, the aim of the present work is to study thechanges induced by TGF-β and the underlying interplay between TGF-β and Notchsignalling on cell populations arising from adult brain SVZ cultures.Wistar rat adult brainSVZ neurospheres were plated in coated coverslips and cultured for 48 h andthen treated with TGF-β for different times. Results obtained 48 h afterplating show a significant increase inthe percentage of glial cell population: PDGFRα+ and GFAP+ cells, concomitantlywith an increase in the expression of Notch ligand, Jagged1. Furthermore, Ki67expression and BrdU incorporation assays rendered a significant increase intotal cell proliferation after 24-h culture and a significant increase in theproportion of PDGFRα+/Ki67. In addition, 8-day cultures exhibited not only asignificant increase in the proportion of MBP+ cells but also a higher degreeof cell differentiation, as evidenced by the presence of more ramifiedprocesses suggesting an effect of TGF-β on differentiation towards a matureoligodendrocyte. TGF-β signaling inhibition resulted in a decrease in Jagged1expression and OPC population; moreover, Notch signaling inhibition showed adecrease in OPC proliferation. Our results demonstrate the participation of Notchsignaling in TGF-β effects on glial cell fate decisions of adult brain SVZNPCs, as well as on OPC proliferation and maturation