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Adenosine A2A receptor (A2A R) activation modulates several brain processes, ranging from neuronal maturation to synaptic plasticity. Most of these actions occur through the modulation of the actions of the neurotrophin brain-derived neurotrophic factor (BDNF). In this work we studied the role of A2A Rs in regulating postnatal and adult neurogenesis in the rat hippocampal dentate gyrus (DG). Here we show that A2A R activation with CGS 21680 promoted neural stem cell self-renewal, protected committed neuronal cells from cell death and co