Activation of A and A 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 A adenosine receptor agonist cyclopentyladenosine (CPA) and the A adenosine receptor agonist CGS-21680 increased proliferation of NPCs. The A adenosine receptor agonist-induced cell proliferation was attenuated by A adenosine receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPA). Accordingly, the A adenosine receptor agonist-induced cell proliferation was attenuated by A 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 A and A adenosine receptor stimulated the proliferation of NPCs via the ERK and Akt signaling pathways.