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塞拉尼米达唑吡啶通过调节氧化亚氮系统消除炎症和应激引起的抑郁样行为。

Selanylimidazopyridine abolishes inflammation- and stress-induced depressive-like behaviors by modulating the oxido-nitrosative system.

机构信息

Technological Development Center, Division of Biotechnology, Neurobiotechology Research Group, Federal University of Pelotas, Pelotas, RS, Brazil.

Center of Chemical, Pharmaceutical and Food Sciences, Laboratory of Clean Organic Synthesis, Federal University of Pelotas, Pelotas, RS, Brazil.

出版信息

Eur J Pharmacol. 2022 Jan 5;914:174570. doi: 10.1016/j.ejphar.2021.174570. Epub 2021 Oct 12.

Abstract

The 3-[(4-methoxyphenyl)selanyl]-2-phenylimidazo[1,2-a] pyridine (MPI), a novel organic selenium compound, has been receiving increased attention due to its antioxidant effects and its ability to protect against depression-like behaviours. However, it remains elusive whether MPI is able to reverse depressive-like symptoms and biochemical alterations in mice. In the present work, we explored the ability of MPI (10 mg/kg, i.g.) to reverse inflammation- and stress-induced depression-like behaviours in mice injected with tumour necrosis factor (TNF-α) or submitted to acute restraint stress. Depression-like behaviours were evaluated by the tail suspension and splash test and the open field test was used to evaluate the locomotor activity of mice. The prefrontal cortex and hippocampus of mice were used for the evaluation of parameters of oxidonitrosative stress. Here, we showed that a single administration of MPI abolished the depressive-like behaviours induced by TNF-α and acute restraint stress. The oxidative and nitrosative stress presented in mice with depression-like behaviours were also decreased by MPI in the prefrontal cortex and hippocampus. Our findings suggest that MPI presents antidepressant-like activity which is associated with the biochemical regulation of oxidative stress in prefrontal cortex and hippocampus of mice, arising as a promising strategy for the management of depressive symptoms.

摘要

3-[(4-甲氧基苯基)硒基]-2-苯基咪唑并[1,2-a]吡啶(MPI)是一种新型有机硒化合物,由于其抗氧化作用以及预防抑郁样行为的能力而受到越来越多的关注。然而,MPI 是否能够逆转抑郁样症状和小鼠的生化改变仍不清楚。在本工作中,我们探讨了 MPI(10mg/kg,ig)是否能够逆转注射肿瘤坏死因子(TNF-α)或急性束缚应激的小鼠的炎症和应激诱导的抑郁样行为。通过悬尾和溅水试验评估抑郁样行为,并用旷场试验评估小鼠的运动活性。使用小鼠的前额叶皮层和海马评估氧化硝化应激的参数。结果表明,MPI 单次给药可消除 TNF-α和急性束缚应激引起的抑郁样行为。MPI 还降低了抑郁样行为小鼠前额叶皮层和海马中的氧化和硝化应激。我们的研究结果表明,MPI 具有抗抑郁样活性,与小鼠前额叶皮层和海马的氧化应激的生化调节有关,为管理抑郁症状提供了一种有前景的策略。

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