Brain-derived neurotrophic factor and adenosine A2A receptor interaction modulates oligodendrogenesis derived from postnatal SVZ neural stem cells

Oligodendrocytes (OLs) are vital for myelin formation in the Central Nervous System. OLs can be produced by the maturation of oligodendrocyte precursor cells (OPCs) present throughout the brain parenchyma or from the differentiation of subventricular zone-derived neural stem cells (SVZ-NSCs). Importantly, efficient differentiation from SVZ-NSCs remains a significant area of research due to its potential for remyelination in demyelinating disorders. In this work, we studied the role of brain-derived neurotrophic factor (BDNF) and adenosine A2A receptors (A2ARs), as well as the putative crosstalk between these two modulatory mechanisms, in regulating oligodendrogenesis from SVZ-NSCs. Using a neurosphere culture system, we observed that BDNF significantly increased the mRNA expression levels of OPC cell markers after 2 days in vitro (DIV), an effect blocked by the A2AR antagonist ZM 241385. This early transcriptional regulation by BDNF was followed by changes in the percentage of both OPCs and mature OLs in culture at DIV 7 and 14. Interestingly, blocking A2ARs prevented the potentiating effect of BDNF on the percentage of OLs at DIV 14. Concerning the morphology of mature OLs, BDNF influenced their maturation by reducing branching near the soma at DIV 7, an effect that was not observed at 14 DIV, when all treatments resulted in similar OL morphology. Overall, our results establish BDNF as a regulator of OL formation from SVZ-NSCs, with A2AR-BDNF interaction modulating the differentiation process.