Oligodendrocytes (OLs) are the myelin-forming cells in the Central Nervous System of vertebrates. The role of Adenosine A2A receptors (A2ARs) and brain-derived neurotrophic factor (BDNF) on adult oligodendrogenesis from subventricular zone neural stem cells (SVZ-NSCs) remains highly unknown. We aimed at studying how these modulators and their putative crosstalk impact OL differentiation from postnatal SVZ-NSCs. For this, C57BL/6 P1-3 mice SVZ-derived neurospheres were pharmacologically exposed to BDNF (30 ng/mL) and ZM 241385 (50 nM), an antagonist for A2ARs. mRNA expression levels of oligodendroglial markers were evaluated by RT-PCR and oligodendroglial differentiation was assessed by immunocytochemistry, both targeting NG2/PDGFRalpha (for oligodendrocyte precursor cells, OPCs) and MBP (for mature OLs). Results show that after 2 days in vitro (DIV), BDNF potentiated mRNA expression levels for OPC markers (N=3, p<0.05), while protein levels remain unaltered (N=3), an effect that was blocked by ZM 241385 (N=3, p<0.05). The effects of BDNF in promoting SVZ-NSCs differentiation into OPCs were maintained throughout DIV 7 (N=9, p<0.001) and DIV 14 (N=3, p<0.01). Moreover, at DIV 14 BDNF also promoted SVZ-NSCs differentiation into mature OLs (N=5, p<0.05), and this effect was blocked by the A2AR antagonist (N=5, p<0.05). In conclusion, BDNF can promote the formation and differentiation of OPCs and OLs derived from SVZ-NSCs in vitro and this effect is blocked by the treatment with an A2AR antagonist. This work outlined a role for BDNF in promoting the formation of OPCs from SVZ-NSCs which may be particularly important in demyelinating disorders.