Neuromolecular and behavioral effects of cannabidiol on depressive-associated behaviors and neuropathic pain conditions in mice

IF 4.6 2区 医学 Q1 NEUROSCIENCES Neuropharmacology Pub Date : 2024-09-06 DOI:10.1016/j.neuropharm.2024.110153
Ziyi Shen , Nana Bao , Junwen Chen , Ming Tang , Linfeng Yang , Yang Yang , Haoran Zhang , Jingyu Han , Peilu Yu , Shushan Zhang , Hanfeng Yang , Guohui Jiang
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Abstract

Background and aims

Neuropathic pain (NP) has a high incidence in the general population, is closely related to anxiety disorders, and has a negative impact on the quality of life. Cannabidiol (CBD), as a natural product, has been extensively studied for its potential therapeutic effects on symptoms such as pain and depression (DP). However, the mechanism of CBD in improving NP with depression is not fully understood.

Methods

First, we used bioinformatics tools to deeply mine the intersection genes associated with NP, DP, and CBD. Secondly, the core targets were screened by Protein-protein interaction network, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes analysis, molecular docking and molecular dynamics simulation. Next, the effects of CBD intervention on pain and depressive behaviors in the spinal nerve ligation (SNL) mouse model were evaluated using behavioral tests, and dose-response curves were plotted. After the optimal intervention dose was determined, the core targets were verified by Western blot (WB) and Quantitative Polymerase Chain Reaction (qPCR). Finally, we investigated the potential mechanism of CBD by Nissl staining, Immunofluorescence (IF) and Transmission Electron Microscopy (TEM).

Results

A total of five core genes of CBD most associated with NP and DP were screened by bioinformatics analysis, including PTGS2, GPR55, SOD1, CYP1A2 and NQO1. Behavioral test results showed that CBD by intraperitoneal administration 5 mg/kg can significantly improve the pain behavior and depressive state of SNL mice. WB, qPCR, IF, and TEM experiments further confirmed the regulatory effects of CBD on key molecules.

Conclusion

In this study, we found five targets of CBD in the treatment of NP with DP. These findings provide further theoretical and experimental basis for CBD as a potential therapeutic agent.

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大麻二酚对小鼠抑郁相关行为和神经病理性疼痛的神经分子和行为影响。
背景和目的:神经性疼痛(NP)在普通人群中发病率很高,与焦虑症密切相关,对生活质量有负面影响。大麻二酚(CBD)作为一种天然产品,其对疼痛和抑郁(DP)等症状的潜在治疗效果已得到广泛研究。然而,人们对大麻二酚改善抑郁症 NP 的机制还不完全了解:首先,我们利用生物信息学工具深入挖掘了与 NP、DP 和 CBD 相关的交叉基因。其次,通过蛋白质-蛋白质相互作用网络、基因本体、京都基因和基因组百科全书分析、分子对接和分子动力学模拟筛选出核心靶点。接着,利用行为测试评估了 CBD 干预对脊神经结扎(SNL)小鼠模型中疼痛和抑郁行为的影响,并绘制了剂量-反应曲线。在确定了最佳干预剂量后,我们通过 Western 印迹(WB)和定量聚合酶链式反应(qPCR)对核心靶点进行了验证。最后,我们通过Nissl染色、免疫荧光(IF)和透射电子显微镜(TEM)研究了CBD的潜在机制:结果:通过生物信息学分析,共筛选出与 NP 和 DP 最相关的五个 CBD 核心基因,包括 PTGS2、GPR55、SOD1、CYP1A2 和 NQO1。行为试验结果表明,CBD腹腔注射5mg/kg可显著改善SNL小鼠的疼痛行为和抑郁状态。WB、qPCR、IF和TEM实验进一步证实了CBD对关键分子的调控作用:本研究发现了 CBD 在 DP 治疗 NP 中的五个靶点。这些发现为 CBD 作为一种潜在的治疗药物提供了进一步的理论和实验依据。
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来源期刊
Neuropharmacology
Neuropharmacology 医学-神经科学
CiteScore
10.00
自引率
4.30%
发文量
288
审稿时长
45 days
期刊介绍: Neuropharmacology publishes high quality, original research and review articles within the discipline of neuroscience, especially articles with a neuropharmacological component. However, papers within any area of neuroscience will be considered. The journal does not usually accept clinical research, although preclinical neuropharmacological studies in humans may be considered. The journal only considers submissions in which the chemical structures and compositions of experimental agents are readily available in the literature or disclosed by the authors in the submitted manuscript. Only in exceptional circumstances will natural products be considered, and then only if the preparation is well defined by scientific means. Neuropharmacology publishes articles of any length (original research and reviews).
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