Guanosine Promotes Proliferation in Neural Stem Cells from Hippocampus and Neurogenesis in Adult Mice

Neural stem cells can generate new neurons in the mouse adult brain in a complex multistep process called neurogenesis. Several factors regulate this process, including neurotransmitters, hormones, neurotrophic factors, pharmacological agents, and environmental factors. Purinergic signaling, mainly the adenosinergic system, takes part in neurogenesis, being involved in cell proliferation, migration, and differentiation. However, the role of the purine nucleoside guanosine in neurogenesis remains unclear. Here, we examined the effect of guanosine by using the neurosphere assay derived from neural stem cells of adult mice. We found that continuous treatment with guanosine increased the number of neurospheres, neural stem cell proliferation, and neuronal differentiation. The effect of guanosine to increase the number of neurospheres was reduced by removing adenosine from the culture medium. We next traced the neurogenic effect of guanosine in vivo. The intraperitoneal treatment of adult C57BL/6 mice with guanosine (8 mg/kg) for 26 days increased the number of dividing bromodeoxyuridine (BrdU)-positive cells and also increased neurogenesis, as identified by measuring doublecortin (DCX)-positive cells in the dentate gyrus (DG) of the hippocampus. Antidepressant-like behavior in adult mice accompanied the guanosine-induced neurogenesis in the DG. These results provide new evidence of a pro-neurogenic effect of guanosine on neural stem/progenitor cells, and it was associated in vivo with antidepressant-like effects.