[1]郭笑迪,张国新,彭琴玉,等.Tau蛋白聚集体促进小胶质细胞活化的机制研究[J].卒中与神经疾病杂志,2023,30(05):429-432,439.[doi:10.3969/j.issn.1007-0478.2023.05.001]
　Guo Xiaodi,Zhang Guoxin,Peng Qinyu,et al.Tau aggregates promote microglia activation[J].Stroke and Nervous Diseases,2023,30(05):429-432,439.[doi:10.3969/j.issn.1007-0478.2023.05.001]
点击复制

Tau蛋白聚集体促进小胶质细胞活化的机制研究()
分享到：

《卒中与神经疾病》杂志[ISSN:1007-0478/CN:42-1402/R]

卷:
第30卷
期数:
2023年05期
页码:
429-432,439
栏目:
阿尔茨海默病
出版日期:
2023-10-20

文章信息/Info

Title:
Tau aggregates promote microglia activation
文章编号:
1007-0478(2023)05-0429-05
作者:
郭笑迪; 张国新; 彭琴玉; 张振涛
430060 武汉大学人民医院神经内科[郭笑迪 张国新 彭琴玉 张振涛(通信作者)]
Author(s):
Guo Xiaodi;  Zhang Guoxin;  Peng Qinyu;  et al.
Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060
关键词:
半乳糖凝集素-9 Tau蛋白 小胶质细胞 炎症因子
Keywords:
Galectin-9 Tau Microglia Inflammatory factors
分类号:
R742
DOI:
10.3969/j.issn.1007-0478.2023.05.001
文献标志码:
A
摘要:
目的 探讨Tau蛋白聚集体对小胶质细胞活化的影响及机制。方法 纯化重组的Tau蛋白并制备Tau聚集体,处理小鼠小胶质细胞(BV2 microglia of mice,BV2),Western blot检测半乳糖凝集素(Galectin,Gal)-9的表达水平,酶联免疫吸附测定(Enzyme linked immunosorbent assay,ELISA)法检测细胞培养基中Gal-9蛋白的水平; 体外表达纯化Gal-9蛋白,处理BV2,Western blot检测细胞中白细胞分化抗原68(Cluster of differentiation 68,CD68)和电离钙结合适配器分子1(Lonized calcium-binding adapter molecule 1,IBA1)蛋白的表达水平; 免疫荧光检测CD68的表达水平; ELISA检测细胞培养基中炎症因子肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)的水平,逆转录-聚合酶链反应(Reverse transcription-Polymerase chain reaction,RT-PCR)检测细胞中TNF-α的转录水平; Tau蛋白聚集体与短发夹RNA(Short hairpin RNA,ShRNA)-Gal-9同时处理BV2,观察阻断Gal-9的作用对小胶质细胞活化的影响。结果 与对照组比较,Tau蛋白聚集体处理BV2引起Gal-9蛋白表达增加,并释放到细胞外; Gal-9蛋白处理BV2导致其活化,CD68和IBA1表达增加; 促炎性细胞因子TNF-α表达增加; 阻断Gal-9的作用可减轻Tau聚集体诱导的小胶质细胞活化。结论 Tau聚集体促进BV2表达Gal-9蛋白,后者诱导小胶质细胞激活和促炎性细胞因子释放。
Abstract:
ObjectiveTo investigate the effect of tau aggregates on microglial activation.Methods BV2 cells were exposed to recombinant tau aggregates. The levels of galectin-9(Gal-9)were detected using Western blot analysis. The levels of Gal-9 in the culture medium were detected by ELISA. Purified Gal-9 was used to treat BV2 cells. The levels of CD68 and IBA1 were analyzed by Western blots. Immunofluorescence was used to detect the expression of CD68. The level of tumor necrosis factor-α(TNF-α)was determined by ELISA. Reverse transcription-Polymerase chain reaction(RT-PCR)was used to assess the mRNA levels of TNF-α. The role of Gal-9 in the activation of microglia was observed by treating BV2 cells with Tau aggregates and ShRNA-Gal-9.Results Compared with the PBS control, Tau PFFs elevated Gal-9 levels in BV2 cells. The levels of Gal-9 in the medium were also increased after treatment with Tau PFFs. Compared with control BV2 cells, the levels of CD68 and IBA1 in BV2 cells were increased in cells exposed to Gal-9, indicating that Gal-9 induces microglial activation. The protein and mRNA levels of the pro-inflammatory factor TNF-α were increased after Gal-9 treatment. Blocking the expression of Gal-9 attenuated the activation of microglia induced by Tau aggregates.Conclusion Tau aggregates promote Gal-9 expression in BV2 cells, which in turn induces microglial activation.

参考文献/References:

[1] Frost JL,Schafer DP.Microglia:architects of the developing nervous system[J].Trends Cell Biol,2016,26(8):587-597.
[2] John S,Mishra R.mRNA transcriptomics of galectins unveils heterogeneous organization in mouse and human brain[J].Front Mol Neurosci,2016:139.
[3] Wang X,Niu Y,Yue CX,et al.Increased ileal bile acid binding protein and galectin-9 are associated with mild cognitive impairment and Alzheimer's disease[J].J Psychiatr Res,2019,119:102-106.
[4] Hansen DV,Hanson JE,Sheng M.Microglia in Alzheimer's disease[J].J Cell Biol,2018,217(2):459-472.
[5] Hong S,Beja-Glasser VF,Nfonoyim BM,et al.Complement and microglia mediate early synapse loss in Alzheimer mouse models[J].Science,2016,352(6286):712-716.
[6] Rmm DA,Afm DE,Olca DE,et al.Alzheimer's disease:is there a role for galectins?[J].Eur J Pharmacol,2021:174437.
[7] Steelman AJ,Li J.Astrocyte galectin-9 potentiates microglial TNF secretion[J].J Neuroinflammation,2014:144.
[8] Bellac CL,Coimbra RS,Simon F,et al.Gene and protein expression of galectin-3 and galectin-9 in experimental pneumococcal meningitis[J].Neurobiol Dis,2007,28(2):175-183.
[9] Steelman AJ,Smith R,Welsh CJ,et al.Galectin-9 protein is up-regulated in astrocytes by tumor necrosis factor and promotes encephalitogenic t-cell apoptosis[J].Journal of Biological Chemistry,2013,288(33):23776-23787.
[10] Burman J,Svenningsson A.Cerebrospinal fluid concentration of Galectin-9 is increased in secondary progressive multiple sclerosis[J].J Neuroimmunol,2016,292:40-44.
[11] Stancic M,van Horssen J,Thijssen VL,et al.Increased expression of distinct galectins in multiple sclerosis lesions[J].Neuropathol Appl Neurobiol,2011,37(6):654-671.
[12] Liu J,Huang S,Lu F.Galectin-3 and galectin-9 May differently regulate the expressions of microglial M1/M2 markers and T helper 1/Th2 cytokines in the brains of genetically susceptible C57BL/6 and resistant BALB/c mice following peroral infection with toxoplasma gondii[J].Front Immunol,2018:1648.
[13] Chen ZQ,Yu H,Li HY,et al.Negative regulation of glial Tim-3 inhibits the secretion of inflammatory factors and modulates microglia to antiinflammatory phenotype after experimental intracerebral hemorrhage in rats[J].CNS Neurosci Ther,2019,25(6):674-684.
[14] Merighi S, Nigro M, Travagli A, et al. Microglia and Alzheimer's Disease [J]. International journal of molecular sciences, 2022, 23(21).

备注/Memo

备注/Memo:
基金项目:国家自然科学基金面上项目(82271447)
更新日期/Last Update: 2023-10-20