Inhibition of Galectin-3 in a Rat Model of Epilepsy and Kainate-Activated BV2 Cells Limits Microglial Activation Through the NLRP3/Pyroptosis Pathway.

IF 2.2 4区医学 Q3 ENDOCRINOLOGY & METABOLISM Neuroimmunomodulation Pub Date : 2023-01-01 Epub Date: 2023-11-03 DOI:10.1159/000534833

Weiwei Sun, Ying Hao, Chunxiang Li, Yuanyuan Zhao, Haishao Yu, Lin Wang

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Abstract

Introduction: This study aimed to investigate the possible role of galectin-3 in epilepsy and further explore its underlying mechanisms.

Methods: Sprague-Dawley rats were intraperitoneally injected with 30 mg/kg pilocarpine to induce an animal model of epilepsy. To inhibit galectin-3, the epilepsy model of rats was intraperitoneally injected with TD139. The severity of the seizure was graded according to the Racine score. The pathological changes in hippocampal CA1 regions were observed by hematoxylin and eosin and Nissl staining. Enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction, and Western blot were used to detect the levels of cytokines and pyroptosis-related factors. The in vitro effects of galectin-3 were confirmed on BV2 cells and rat primary microglia by transfection with lentivirus vectors carrying Lgals3 shRNA or by treatment with TD139.

Results: A higher expression of galectin-3 was observed in the hippocampal CA1 regions of epilepsy rats than in sham rats. Inhibition of galectin-3 by administration of TD139 improved the severity of the seizure, hippocampal damage, and neuron loss. TD139 administration suppressed the expression of NLRP3, ASC, c-caspase-1, and GSDMD-N, and reduced the levels of cytokines. In kainic acid-treated microglia, Lgals3 shRNA or TD139 significantly inhibited Iba1 expression and limited NLRP3/pyroptosis-triggered inflammation.

Conclusion: Galectin-3 activates the NLRP3/pyroptosis signaling pathway to promote microglial activation and neuroinflammation during epilepsy disease progression.

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癫痫大鼠模型中半乳糖凝集素-3的抑制和红藻氨酸激活的BV-2细胞通过NLRP3/焦下垂途径限制小胶质细胞的激活。

引言：本研究旨在探讨半乳糖凝集素-3在癫痫中的可能作用，并进一步探讨其潜在机制。方法：Sprague-Dawley大鼠腹腔注射毛果芸香碱30mg/kg，建立癫痫动物模型。为了抑制半乳糖凝集素-3，大鼠癫痫模型腹膜内注射TD139。根据拉辛评分对癫痫发作的严重程度进行分级。苏木精、伊红和尼氏染色观察海马CA1区的病理变化。采用酶联免疫吸附法、实时定量聚合酶链式反应和蛋白质印迹法检测细胞因子和pyroptosis相关因子的水平。通过携带Lgals3 shRNA的慢病毒载体转染或TD139处理，证实了半乳糖凝集素-3对BV2细胞和大鼠原代小胶质细胞的体外作用。结果：癫痫大鼠海马CA1区半乳糖凝集素3的表达高于假手术大鼠。通过给予TD139抑制半乳糖凝集素-3可改善癫痫发作、海马损伤和神经元损失的严重程度。TD139给药抑制了NLRP3、ASC、c-胱天蛋白酶-1和GSDMD-N的表达，并降低了细胞因子水平。在红藻氨酸处理的小胶质细胞中，Lgals3 shRNA或TD139显著抑制Iba1的表达，并限制NLRP3/焦下垂引发的炎症。结论：半乳糖凝集素-3激活NLRP3/pyroposis信号通路，在癫痫疾病进展过程中促进小胶质细胞活化和神经炎症。

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来源期刊

Neuroimmunomodulation 医学-免疫学

CiteScore

3.60

自引率

4.20%

发文量

审稿时长

>12 weeks

期刊介绍： The rapidly expanding area of research known as neuroimmunomodulation explores the way in which the nervous system interacts with the immune system via neural, hormonal, and paracrine actions. Encompassing both basic and clinical research, ''Neuroimmunomodulation'' reports on all aspects of these interactions. Basic investigations consider all neural and humoral networks from molecular genetics through cell regulation to integrative systems of the body. The journal also aims to clarify the basic mechanisms involved in the pathogenesis of the CNS pathology in AIDS patients and in various neurodegenerative diseases. Although primarily devoted to research articles, timely reviews are published on a regular basis.