Bettio Luis E B, Freitas Andiara E, Neis Vivian B, Santos Danúbia B, Ribeiro Camille M, Rosa Priscila B, Farina Marcelo, Rodrigues Ana Lúcia S
Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Campus Universitário - Trindade, 88040-900, Florianópolis, SC, Brazil.
Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Campus Universitário - Trindade, 88040-900, Florianópolis, SC, Brazil.
Pharmacol Biochem Behav. 2014 Dec;127:7-14. doi: 10.1016/j.pbb.2014.10.002. Epub 2014 Oct 12.
Guanosine is a guanine-based purine that modulates glutamate uptake and exerts neurotrophic and neuroprotective effects. In a previous study, our group demonstrated that this endogenous nucleoside displays antidepressant-like properties in a predictive animal model. Based on the role of oxidative stress in modulating depressive disorders as well as on the association between the neuroprotective and antioxidant properties of guanosine, here we investigated if its antidepressant-like effect is accompanied by a modulation of hippocampal oxidant/antioxidant parameters. Adult Swiss mice were submitted to an acute restraint stress protocol, which is known to cause behavioral changes that are associated with neuronal oxidative damage. Animals submitted to ARS exhibited an increased immobility time in the forced swimming test (FST) and the administration of guanosine (5mg/kg, p.o.) or fluoxetine (10mg/kg, p.o., positive control) before the exposure to stressor prevented this alteration. Moreover, the significantly increased levels of hippocampal malondialdehyde (MDA; an indicator of lipid peroxidation), induced by ARS were not observed in stressed mice treated with guanosine. Although no changes were found in the hippocampal levels of reduced glutathione (GSH), the group submitted to ARS procedure presented enhanced glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD) activities and reduced catalase (CAT) activity in the hippocampus. Guanosine was able to prevent the alterations in GPx, GR, CAT activities, and in SOD/CAT activity ratio, but potentiated the increase in SOD activity elicited by ARS. Altogether, the present findings indicate that the observed antidepressant-like effects of guanosine might be related, at least in part, to its capability of modulating antioxidant defenses and mitigating hippocampal oxidative damage induced by ARS.
鸟苷是一种基于鸟嘌呤的嘌呤，可调节谷氨酸摄取，并发挥神经营养和神经保护作用。在先前的一项研究中，我们团队证明了这种内源性核苷在一种预测性动物模型中具有类抗抑郁特性。基于氧化应激在调节抑郁症中的作用以及鸟苷的神经保护和抗氧化特性之间的关联，在此我们研究了其类抗抑郁作用是否伴随着海马氧化/抗氧化参数的调节。成年瑞士小鼠接受急性束缚应激方案，已知该方案会导致与神经元氧化损伤相关的行为变化。接受急性束缚应激的动物在强迫游泳试验（FST）中静止不动时间增加，而在暴露于应激源之前给予鸟苷（5mg/kg，口服）或氟西汀（10mg/kg，口服，阳性对照）可防止这种改变。此外，在接受鸟苷治疗的应激小鼠中未观察到由急性束缚应激诱导的海马丙二醛（MDA；脂质过氧化指标）水平显著升高。尽管海马中还原型谷胱甘肽（GSH）水平未发现变化，但接受急性束缚应激方案的组海马中谷胱甘肽过氧化物酶（GPx）、谷胱甘肽还原酶（GR）、超氧化物歧化酶（SOD）活性增强，过氧化氢酶（CAT）活性降低。鸟苷能够防止GPx、GR、CAT活性以及SOD/CAT活性比值的改变，但增强了急性束缚应激引起的SOD活性增加。总之，目前的研究结果表明，观察到的鸟苷类抗抑郁作用可能至少部分与其调节抗氧化防御和减轻急性束缚应激诱导的海马氧化损伤的能力有关。
