Activation of A1 and A2a adenosine receptors promotes neural progenitor cell proliferation.

Neural progenitor cells (NPCs) play a key role not only in the maintenance of the adult central nervous system (CNS) but also in the ability to recover from injury and disease. In this study, we established a 96-well-based screening system to screen small molecules modulating the proliferation of NPCs. A compound library composed of 1280 compounds was screened. We found that the A1 adenosine receptor agonist cyclopentyladenosine (CPA) and the A2a adenosine receptor agonist CGS-21680 increased proliferation of NPCs. The A1 adenosine receptor agonist-induced cell proliferation was attenuated by A1 adenosine receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPA). Accordingly, the A2a adenosine receptor agonist-induced cell proliferation was attenuated by A2a adenosine receptor antagonist SCH-58261. Further study indicated that CPA and CGS-21680 treatment induced phosphorylation of extracellular signal-regulated kinase (ERK) and Akt, and CPA-induced or CGS-21680-induced cell proliferation was inhibited by ERK and Akt inhibitors. These results suggested that the activation of A1 and A2a adenosine receptor stimulated the proliferation of NPCs via the ERK and Akt signaling pathways.