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选择性α7烟碱型乙酰胆碱受体刺激对少突胶质细胞的影响:在神经炎症中的潜在意义。

Effects of Selective α7 Nicotinic Acetylcholine Receptor Stimulation in Oligodendrocytes: Putative Implication in Neuroinflammation.

作者信息

Guerriero Claudia, Puliatti Giulia, Di Marino Tamara, Scanavino Giulia, Matera Carlo, Dallanoce Clelia, Tata Ada Maria

机构信息

Department of Biology and Biotechnologies, Sapienza University of Rome, Piazzale A. Moro 5, 00185 Rome, Italy.

Department of Pharmaceutical Sciences, University of Milan, 20133 Milan, Italy.

出版信息

Cells. 2025 Jun 20;14(13):948. doi: 10.3390/cells14130948.

Abstract

UNLABELLED

α7 nAChRs are known to modulate several physiological and pathological functions in glial cells, and their selective activation might have anti-inflammatory effects in the central and peripheral nervous system. OL progenitors (OPCs) respond to cholinergic stimuli via muscarinic receptors that are mainly involved in the modulation of their proliferation. Conversely, the role of nicotinic receptors, particularly α7 nAChRs, has been poorly investigated. In this study, we evaluated the expression of α7 nAChRs in a model of OPCs (Oli neu) and the potential effects mediated by their selective activation.

METHODS

Oli neu cells were used as a murine immortalized OPCs model. The effects of α7 nAChRs stimulation on cell proliferation and survival were assessed by the MTT assay. RT-PCR and Western blot analysis were used to analyze the expression of α7 nAChRs and proliferative and differentiative markers (PCNA, MBP). LPS exposure was used to induce the environment in which the antioxidant and anti-inflammatory properties of α7 nAChRs were analyzed, evaluating NFR2 and TNF-α expression, ROS levels through DCFDA staining while Oil Red O staining was used for the analysis of lipid droplet content as a marker of cellular inflammation response.

RESULTS

The α7 nAChR is expressed both in OPCs and OLs, and its stimulation by the selective agonist ICH3 increases cell proliferation without modifying the OLs' differentiation capability. Moreover, ICH3 showed anti-inflammatory and antioxidant effects against LPS exposure.

CONCLUSIONS

The results herein obtained confirm the role of α7 nAChR in the modulation of neuroinflammatory processes as well as their protective effects on OLs.

摘要

未标记

已知α7烟碱型乙酰胆碱受体(α7 nAChRs)可调节神经胶质细胞的多种生理和病理功能,其选择性激活可能在中枢和外周神经系统中具有抗炎作用。少突胶质前体细胞(OPCs)通过主要参与调节其增殖的毒蕈碱受体对胆碱能刺激作出反应。相反,烟碱型受体,特别是α7 nAChRs的作用尚未得到充分研究。在本研究中,我们评估了α7 nAChRs在OPCs模型(Oli neu)中的表达以及其选择性激活介导的潜在作用。

方法

使用Oli neu细胞作为小鼠永生化OPCs模型。通过MTT法评估α7 nAChRs刺激对细胞增殖和存活的影响。采用RT-PCR和蛋白质印迹分析来分析α7 nAChRs以及增殖和分化标志物(PCNA、MBP)的表达。通过暴露于脂多糖(LPS)来诱导分析α7 nAChRs抗氧化和抗炎特性的环境,评估核因子E2相关因子2(NFR2)和肿瘤坏死因子-α(TNF-α)的表达,通过2',7'-二氯二氢荧光素二乙酸酯(DCFDA)染色评估活性氧(ROS)水平,同时使用油红O染色分析脂滴含量作为细胞炎症反应的标志物。

结果

α7 nAChR在OPCs和少突胶质细胞(OLs)中均有表达,其选择性激动剂ICH3对其刺激可增加细胞增殖,而不改变OLs的分化能力。此外,ICH3对LPS暴露显示出抗炎和抗氧化作用。

结论

本文获得的结果证实了α7 nAChR在调节神经炎症过程中的作用及其对OLs的保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/766e/12248911/2adb9f2eac25/cells-14-00948-g001.jpg

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