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.

神经干细胞可以通过称为神经发生的复杂多步骤过程在小鼠成年大脑中产生新的神经元。有几个因素调节这一过程，包括神经递质，激素，神经营养因子，药理作用剂和环境因子。嘌呤能信号传导，主要是腺苷能系统，参与神经发生，参与细胞增殖，迁移和分化。然而，嘌呤核苷鸟苷在神经发生中的作用仍不清楚。在这里，我们通过使用成年小鼠神经干细胞衍生的神经球测定法检查了鸟苷的作用。我们发现用鸟苷连续治疗可增加神经球数量，神经干细胞增殖和神经元分化。通过从培养基中除去腺苷，降低了鸟苷增加神经球数量的作用。接下来，我们追踪了鸟嘌呤在体内的神经源性作用。通过测量鸟嘌呤（8 mg / kg）腹腔内成年C57BL / 6小鼠的腹腔内治疗26天，增加了分裂的溴脱氧尿苷（BrdU）阳性细胞的数量，并且还增加了神经发生，这是通过测量双肾上腺皮质激素（DCX）阳性细胞来确定的。海马的齿状回（DG）。成年小鼠的抗抑郁样行为伴随着鸟嘌呤诱导的DG神经发生。这些结果提供了鸟苷对神经干/祖细胞的促神经原作用的新证据，并且它在体内与抗抑郁样作用有关。通过测量鸟嘌呤（8 mg / kg）腹腔内成年C57BL / 6小鼠的腹腔内治疗26天，增加了分裂的溴脱氧尿苷（BrdU）阳性细胞的数量，并且还增加了神经发生，这是通过测量双肾上腺皮质激素（DCX）阳性细胞来确定的。海马的齿状回（DG）。成年小鼠的抗抑郁样行为伴随着鸟嘌呤诱导的DG神经发生。这些结果提供了鸟苷对神经干/祖细胞的促神经原作用的新证据，并且它在体内与抗抑郁样作用有关。通过测量鸟嘌呤（8 mg / kg）腹腔内成年C57BL / 6小鼠的腹腔内治疗26天，增加了分裂的溴脱氧尿苷（BrdU）阳性细胞的数量，并且还增加了神经发生，这是通过测量双肾上腺皮质激素（DCX）阳性细胞来确定的。海马的齿状回（DG）。成年小鼠的抗抑郁样行为伴随着鸟嘌呤诱导的DG神经发生。这些结果提供了鸟苷对神经干/祖细胞的促神经原作用的新证据，并且它在体内与抗抑郁样作用有关。通过测量海马齿状回（DG）中的双皮质素（DCX）阳性细胞来确定。成年小鼠的抗抑郁样行为伴随着鸟嘌呤诱导的DG神经发生。这些结果提供了鸟苷对神经干/祖细胞的促神经原作用的新证据，并且它在体内与抗抑郁样作用有关。通过测量海马齿状回（DG）中的双皮质素（DCX）阳性细胞来确定。成年小鼠的抗抑郁样行为伴随着鸟嘌呤诱导的DG神经发生。这些结果提供了鸟苷对神经干/祖细胞的促神经原作用的新证据，并且它在体内与抗抑郁样作用有关。