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首页> 外文期刊>The European Journal of Neuroscience >The antidepressant-like effect of chronic guanosine treatment is associated with increased hippocampal neuronal differentiation
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The antidepressant-like effect of chronic guanosine treatment is associated with increased hippocampal neuronal differentiation

机译：慢性鸟苷治疗的抗抑郁样作用与海马神经元分化增加有关

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Guanosine is a purine nucleoside that occurs naturally in the central nervous system, exerting trophic effects. Given its neuroprotective properties, the potential of guanosine as an antidepressant has been recently examined. Within this context, the present study sought to investigate the effects of chronic treatment with guanosine on the tail suspension test (TST), open field test and adult hippocampal neurogenesis. Swiss mice were administered guanosine for 21days (5mg/kg/day, p.o.) and subsequently submitted to the TST and open-field test. Following behavioural testing, animals were killed and the brains were processed for immunohistochemical analyses of hippocampal cell proliferation and neuronal differentiation. Animals treated with guanosine showed a reduction in immobility time in the TST without alterations in locomotor activity, confirming the antidepressant-like effect of this compound. Quantitative microscopic analysis did not reveal significant alterations in the numbers of Ki-67- and proliferating cell nuclear antigen (PCNA)-positive cells in the hippocampal dentate gyrus (DG) of guanosine-treated mice. However, guanosine treatment resulted in a significant increase in the number of immature neurons, as assessed by immunohistochemistry for the neurogenic differentiation protein. Interestingly, this effect was localized to the ventral hippocampal DG, a functionally distinct region of this structure known to regulate emotional and motivational behaviours. Taken together, our results suggest that the antidepressant-like effect of chronic guanosine treatment is associated with an increase in neuronal differentiation, reinforcing the notion that this nucleoside may be an endogenous mood modulator.
机译：鸟苷是一种嘌呤核苷，天然存在于中枢神经系统中，发挥营养作用。鉴于其神经保护特性，最近已研究了鸟苷作为抗抑郁药的潜力。在这种情况下，本研究试图研究鸟嘌呤长期治疗对尾部悬吊试验（TST），开放视野试验和成年海马神经发生的影响。给瑞士小鼠施用鸟嘌呤21天（5mg / kg /天，口服），随后接受TST和开放视野测试。在进行行为测试后，将动物处死并对其大脑进行处理，以进行海马细胞增殖和神经元分化的免疫组织化学分析。用鸟苷处理的动物在TST中的固定时间减少，而运动活性没有改变，证实了该化合物的抗抑郁样作用。定量显微镜分析未发现鸟嘌呤治疗的小鼠海马齿状回（DG）Ki-67和增殖细胞核抗原（PCNA）阳性细胞数量发生显着变化。然而，如对神经原性分化蛋白的免疫组织化学所评估的，鸟苷治疗导致未成熟神经元的数量显着增加。有趣的是，这种作用局限于腹侧海马DG，该结构的功能不同区域已知调节情绪和动机行为。两者合计，我们的结果表明，慢性鸟苷治疗的抗抑郁样作用与神经元分化的增加有关，强化了这种核苷可能是内源性情绪调节剂的观念。

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