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Repeated Nitrous Oxide Exposure Exerts Antidepressant-Like Effects Through Neuronal Nitric Oxide Synthase Activation in the Medial Prefrontal Cortex
Frontiers in Psychiatry ( IF 3.2 ) Pub Date : 2020-07-31 , DOI: 10.3389/fpsyt.2020.00837
Wei Liu , Qian Li , Binglu Ye , Hang Cao , Fuyi Shen , Zhendong Xu , Weijia Du , Fei Guo , Jinqi Liu , Tianyu Li , Bing Zhang , Zhiqiang Liu

Clinical studies have demonstrated that exposure to the inhalational general anesthetic nitrous oxide (N2O) produces antidepressant effects in depressed patients. However, the mechanisms underlying the antidepressant effects of N2O remain largely unknown. Neuronal nitric oxide synthase (nNOS)–mediated nitric oxide (NO) synthesis is essential for brain function and underlies the molecular mechanisms of many neuromodulators. We hypothesized that activation of the nNOS/NO pathway in the medial prefrontal cortex (mPFC) might mediate the antidepressant effects of N2O. In this study, we revealed that repeated N2O exposure produced antidepressant-like responses in mice. Our mechanistic exploration showed that repeated N2O exposure increased burst firing activity and that the expression levels of BDNF with nNOS activation were dependent in the mPFC. In particular, the antidepressant-like effects of N2O were also antagonized by local nNOS inhibition in the mPFC. In summary, our results indicated that N2O exposure enhances BDNF expression levels and burst firing rates in an nNOS activation dependent manner, which might underlie the pharmacological mechanism of the antidepressant-like effects of N2O exposure. The present study appears to provide further mechanistic evidence supporting the antidepressant effects of N2O.



中文翻译:

反复暴露于一氧化二氮可通过内侧额额叶皮层中的神经元一氧化氮合酶活化而产生抗抑郁样作用

临床研究表明,接触吸入性全身麻醉剂一氧化二氮(N 2 O)对抑郁症患者产生抗抑郁作用。然而,N 2 O的抗抑郁作用的潜在机制仍是未知之数。神经元一氧化氮合酶(nNOS)介导的一氧化氮(NO)合成对于大脑功能至关重要,并且是许多神经调节剂的分子机制的基础。我们假设内侧前额叶皮层(mPFC)中nNOS / NO途径的激活可能介导N 2 O的抗抑郁作用。在这项研究中,我们揭示了重复的N 2 O暴露可在小鼠中产生抗抑郁样反应。我们的机理研究表明,重复的N 2O暴露增加了爆发射击活性,并且具有nNOS激活的BDNF的表达水平取决于mPFC。尤其是,mPFC中的局部nNOS抑制作用也可拮抗N 2 O的抗抑郁样作用。总之,我们的结果表明,N 2 O暴露以nNOS激活依赖性方式增强BDNF表达水平和爆发率,这可能是N 2 O暴露抗抑郁样作用的药理机制的基础。本研究似乎为支持N 2 O的抗抑郁作用提供了进一步的机理证据。

更新日期:2020-09-03
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