Tropisetron attenuated the anxiogenic effects of social isolation by modulating nitrergic system and mitochondrial function
Tropisetron attenuated the anxiogenic effects of social isolation by modulating nitrergic system and mitochondrial function
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DOI：
10.1016/j.bbagen.2015.09.009
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发表时间：
2015-12-01
影响因子：
3
通讯作者：
Hosseini, Mir-Jamal
中科院分区：
文献类型：
--
作者：
Amiri, Shayan;Amini-Khoei, Hossein;Hosseini, Mir-Jamal
背景：早期社会隔离应激（SIS）与焦虑行为的发生有关。氮能系统和线粒体功能之间的相互作用似乎在介导焦虑样行为中起作用。在这项研究中，我们的目的是研究托烷司琼的抗焦虑作用在SIS的动物模型，我们试图说明氮能系统和线粒体function.Methods的可能作用：我们采用早期社会隔离范式的雄性NMRI小鼠。采用高架十字迷宫、旷场试验和洞板试验等有效的行为学测试方法，观察不同剂量托烷司琼、一氧化氮药物或二者联合治疗对成年期动物焦虑样行为的影响。住房条件和药物治疗对线粒体功能的影响进行了研究，在海马通过评估ATP，GSH，ROS和亚硝酸盐levels.Results：早期SIS的致炎作用进行了评估，在海马，OFT，和HBT。此外，SIS破坏线粒体功能，并引起应激动物海马体的氧化应激。托烷司琼在应激小鼠中显示出抗焦虑作用。这些作用也是由氮能系统通过影响线粒体功能和调节氧化应激而介导的。L-精氨酸，一氧化氮的前体，取消了托烷司琼的抗焦虑作用的行为tasks.Conclusions和一般意义的任务，并阻止它对线粒体和氧化challenge. Conclusions的保护作用：我们的研究结果表明托烷司琼衰减焦虑的影响，SIS减轻一氧化氮对线粒体功能的负面影响。(C)2015爱思唯尔B. V.保留所有权利。
Background: Early social isolation stress (SIS) is associated with the occurrence of anxiety behaviors. It seems interaction between the nitrergic system and mitochondrial function plays a role in mediating the anxiety-like behaviors. In this study, we aimed to investigate the anxiolytic effects of tropisetron in animal model of SIS and we try to illustrate the possible role of nitrergic system and mitochondrial function.Methods: We applied early social isolation paradigm to male NMRI mice. Animals treated with various doses of tropisetron, nitric oxide agents or their combination and anxiety-like behaviors of animals were assessed using valid behavioral tests including elevated plus maze (EPM), open-field test (OFT) and hole-board test (HBT) in their adulthood. Effects of housing conditions and drug treatments on the mitochondrial function were investigated in the hippocampus by assessing the ATP, GSH, ROS and nitrite levels.Results: Anxiogenic effects of early SIS were assessed in the EPM, OFT, and HBT. Also, SIS disrupted mitochondrial function and caused oxidative stress in the hippocampus of stressed animals. Tropisetron showed an anxiolytic effect in the stressed mice. Also, these effects were mediated by nitrergic system by affecting mitochondrial function and modulating the oxidative stress. L-arginine, a nitric oxide precursor, abolished the anxiolytic effects of tropisetron in the behavioral tasks and blocked the protective effects of it against mitochondrial and oxidative challenge.Conclusions and general significance: Our results demonstrated tropisetron attenuated the anxiogenic effects of SIS by mitigation of the negative effects of nitric oxide on mitochondrial function. (C) 2015 Elsevier B.V. All rights reserved.