米那西普兰和香兰素缓解利血平诱导大鼠纤维肌痛相关抑郁:Wnt/β-Catenin信号通路的作用

IF 4.6 2区 医学 Q1 NEUROSCIENCES
Molecular Neurobiology Pub Date : 2025-06-01 Epub Date: 2025-02-10 DOI:10.1007/s12035-025-04723-w
Nour A Kamaly, Ahmed S Kamel, Nermin Abdelhamid Sadik, Nancy N Shahin
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引用次数: 0

摘要

纤维肌痛(FM)患者极易患抑郁症。在几项研究中,Wnt/β-连环蛋白信号在对抗抑郁症中发挥了至关重要的作用。fda批准的FM药物milnacipran (Miln)已显示出抗FM的潜力。然而,尚无研究调查其在FM中的抗抑郁作用。香兰素(Van)是一种众所周知的植物化学物质,通常被用作调味剂,以前在几种动物模型中报道过其抗抑郁和抗伤害性作用,但迄今尚未在FM中进行过测试。本研究通过研究Wnt/β-catenin信号通路,探讨Van和Miln在FM中的抗抑郁作用。雌性Wistar大鼠注射利血平(1 mg/kg/d s.c)诱导FM,持续3 d。随后的14天,动物分别服用Miln (30 mg/kg/day p.o)或Van (100 mg/kg/day p.o)。结果显示,两种药物在强迫游泳试验中除具有镇痛作用外,均有抗抑郁作用,在Randall-Selitto、热板、冷异常性、Von-Frey和尾浸试验中均有抗异动作用。生物化学方面,Miln和Van显著增强了海马中血清素能的传递,上调了Wnt/GSK-3β/β-catenin信号轴的蛋白表达,包括下游蛋白、T细胞因子和dicer。随后,韧性微核糖核酸(miRNAs) 124和135上调。组织病理学检查证实了生化和分子的发现。有趣的是,通过给药β-连环蛋白抑制剂XAV939 (0.1 mg/kg,每日1次),Miln和Van的这些作用被推翻。综上所述,本研究通过激活利血平诱导的FM海马区Wnt/β-catenin信号,概述了Miln和Van的抗抑郁倾向。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Milnacipran and Vanillin Alleviate Fibromyalgia-Associated Depression in Reserpine-Induced Rat Model: Role of Wnt/β-Catenin Signaling.

Fibromyalgia (FM) patients are highly susceptible to depression. Wnt/β-catenin signaling has shown a crucial role against depression in several studies. The FDA-approved FM drug, milnacipran (Miln), has shown antinociceptive potential against FM. Yet, no study has investigated its antidepressant potential in FM. Vanillin (Van), a well-known phytochemical often employed as flavoring agent, has been previously reported for its antidepressant and antinociceptive effects in several animal models, but has not been tested so far in FM. This study explored the antidepressant effect of Van and Miln in FM through investigating Wnt/β-catenin signaling. FM was induced in female Wistar rats by injecting reserpine (1 mg/kg/day s.c) for 3 days. Thereafter, animals received either Miln (30 mg/kg/day p.o) or Van (100 mg/kg/day p.o) for the subsequent 14 days. Results showed that both drugs demonstrated antidepressant effect in forced swimming test besides analgesic, and antiallodynic influences observed in Randall-Selitto, hot plate, cold allodynia, Von-Frey, and tail immersion tests. Biochemically, Miln and Van significantly enhanced serotonergic transmission in the hippocampus and upregulated the protein expression of the Wnt/GSK-3β/β-catenin signaling axis, including the downstream proteins, T cell factor, and dicer. This is followed by subsequent upregulation of the resilience micro ribonucleic acids (miRNAs) 124 and 135. Histopathological examinations corroborated the biochemical and molecular findings. Interestingly, these effects of Miln and Van were overturned via administration of the β-catenin inhibitor, XAV939 (0.1 mg/kg, i.p., daily). In conclusion, this study outlined the antidepressant aptitude of Miln and Van through activating Wnt/β-catenin signaling in the hippocampus in reserpine-induced FM.

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来源期刊
Molecular Neurobiology
Molecular Neurobiology 医学-神经科学
CiteScore
9.00
自引率
2.00%
发文量
480
审稿时长
1 months
期刊介绍: Molecular Neurobiology is an exciting journal for neuroscientists needing to stay in close touch with progress at the forefront of molecular brain research today. It is an especially important periodical for graduate students and "postdocs," specifically designed to synthesize and critically assess research trends for all neuroscientists hoping to stay active at the cutting edge of this dramatically developing area. This journal has proven to be crucial in departmental libraries, serving as essential reading for every committed neuroscientist who is striving to keep abreast of all rapid developments in a forefront field. Most recent significant advances in experimental and clinical neuroscience have been occurring at the molecular level. Until now, there has been no journal devoted to looking closely at this fragmented literature in a critical, coherent fashion. Each submission is thoroughly analyzed by scientists and clinicians internationally renowned for their special competence in the areas treated.
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