IF 5.2 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Barbara Chruścicka-Smaga, Magdalena Sowa-Kućma, Patrycja Pańczyszyn-Trzewik, Bartosz Bobula, Agata Korlatowicz, Katarzyna Latocha, Paulina Pabian, Ewelina Czechowska, Tomasz Lenda, Agata Faron-Górecka, Katarzyna Stachowicz
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引用次数: 0

摘要

焦虑是一种严重的社会问题。它是一种疾病实体,可单独发生或伴随其他疾病,如抑郁症、恐惧症或创伤后应激障碍。我们早期的研究表明,通过抑制环氧化酶-2(COX-2)酶阻断花生四烯酸(AA)通路可调节 mGluRs 诱导的焦虑样行为。在此,我们假设在调节 mGluR7 信号传导的同时调节 AA 通路中的一种成分--2-arachidoglycerol (2-AG),应该足以引发试验生物的类似反应。由于 2-AG 是 CB1 受体的内源性激动剂,我们使用了 CB1/GPR55/μ-opioid 受体拮抗剂(AM251)单独或与 mGluR7 异位激动剂(AMN082)联合使用。应激诱导高热(SIH)试验作为行为读数。AM251 对 AMN082 介导的 CD-1 小鼠 SIH 有双重作用。此外,CB1 受体配体还影响了小鼠在重复 SIH 过程中对压力的适应以及在巴恩斯迷宫中的学习能力。我们还发现,小鼠暴露于 AM251 后,前额叶皮层(PFC)中的 mGluR7 蛋白表达水平发生了变化,这表明 AM251 有可能减轻 AMN082 诱导的 mGluR7 水平下降。AM251对AMN082介导的行为和生化效应所引起的变化在电生理实验中得到了证实,AM251取消了AMN082介导的PFC LTP升级。为了排除 mGluR7 直接参与 AM251 的活性,我们使用了过表达 mGluR7 的细胞系。所有上述结果以及在特定脑区检测到的 CB1 和 mGlu7 受体共定位都有力地表明了 CB1 和 mGlu7 受体之间的特异性相互作用及其信号传导。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Evidence for functional interaction between the CB1 and the mGlu7 receptors mediated signaling in modulation of anxiety behavior and cognition.

Anxiety is a severe social problem. It is a disease entity that occurs alone or accompanies other diseases such as depression, phobia, or post-traumatic stress disorder. Our earlier studies demonstrated that blockage of arachidonic acid (AA) pathway via inhibition of cyclooxygenase-2 (COX-2) enzyme can modulate mGluRs-induced anxiety-like behavior. Here, we hypothesized that modulation of 2-arachidoglycerol (2-AG), a component of the AA pathway, concomitantly with modulation of mGluR7 signaling, should be adequate to trigger a similar response from the test organism. Since 2-AG is an endogenous agonist for CB1 receptors, we used a CB1/GPR55/μ-opioid receptor antagonist (AM251) alone and in combination with mGluR7 allosteric agonist (AMN082). Stress-induced hyperthermia (SIH) test was performed as a behavioral readout. AM251 has a dual mode on AMN082-mediated effects in SIH in CD-1 mice. Furthermore, the CB1 receptor ligand influenced adaptation to stress in repeated SIH procedures and learning possibilities of mice in the Barnes maze. We also found changes in mGluR7 protein expression levels in the prefrontal cortex (PFC) after mice were exposed to AM251, which showed the potential to attenuate the AMN082-induced decline in mGluR7 levels. The changes induced by AM251 on AMN082-mediated behavioral and biochemical effects were confirmed in electrophysiological experiments in which AM251 abolished AMN082-mediated LTP escalation in PFC. The mGluR7 overexpressed cell line was used to exclude the direct involvement of mGluR7 in AM251 activity. All the above results and the co-localization of CB1 and mGlu7 receptors detected in specific brain regions strongly suggest the specific interaction between CB1 and mGlu7 receptors and their signaling.

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来源期刊
Life sciences
Life sciences 医学-药学
CiteScore
12.20
自引率
1.60%
发文量
841
审稿时长
6 months
期刊介绍: Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.
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