SARS-CoV-2感染对人脑小胶质细胞和星形胶质细胞不同亚型的特异性影响

doi:10.16352/j.issn.1001-6325.2025.07.0933

基础医学与临床 ›› 2025, Vol. 45 ›› Issue (7): 933-938.doi: 10.16352/j.issn.1001-6325.2025.07.0933

SARS-CoV-2感染对人脑小胶质细胞和星形胶质细胞不同亚型的特异性影响

金忠满, 韦晖^*

中国医学科学院基础医学研究所北京协和医学院基础学院重大疾病共性机制研究全国重点实验室,北京 100005

收稿日期:2025-03-31 修回日期:2025-04-23 出版日期:2025-07-05 发布日期:2025-06-24
通讯作者: ^*hui.wei@ibms.pumc.edu.cn
基金资助:
科技创新2030-“脑科学与类脑研究”重大项目(021ZD0200600)

Specific effects of SARS-CoV-2 infection on different subtypes of microglia and astrocytes in human brain

JIN Zhongman, WEI Hui^*

State Key Laboratory of Common Mechanism Research for Major Disease, Institute of Basic Medical Sciences CAMS, School of Basic Medicine PUMC, Beijing 100005, China

Received:2025-03-31 Revised:2025-04-23 Online:2025-07-05 Published:2025-06-24
Contact: ^*hui.wei@ibms.pumc.edu.cn

摘要/Abstract

摘要： 目的探讨严重急性呼吸综合征冠状病毒 2型(SARS-CoV-2)感染对人脑小胶质细胞和星形胶质细胞不同表型的影响,揭示其在新型冠状病毒病(COVID-19)相关神经系统症状中的作用。方法选取14例人脑海马—内嗅皮层(HP-EC)样本,包括7例COVID-19患者和7例对照组捐献者,采用多重免疫组化技术检测小胶质细胞和星形胶质细胞的相关标志物,并进行定量与统计学分析。结果 SARS-CoV-2感染显著改变了小胶质细胞和星形胶质细胞在HP-EC各区域的密度。具体表现为神经保护性的星形胶质细胞、神经毒性的星形胶质细胞和调节水稳态的星形胶质细胞密度降低,而吞噬表型的小胶质细胞、趋化表型的小胶质细胞和脂转运表型的星形胶质细胞则出现区域特异性的密度改变。结论 SARS-CoV-2感染对中枢神经系统免疫微环境产生深刻影响,可能通过改变小胶质细胞和星形胶质细胞的功能状态,参与COVID-19相关神经系统症状的发病机制。

关键词: SARS-CoV-2, 小胶质细胞, 星形胶质细胞, 多重免疫组化

Abstract: Objective To investigate the impact of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) infections on different phenotypes of microglia and astrocytes in the human brain and their role in neurological symptoms resulted from COVID-19 infection. Methods Fourteen human hippocampus-entorhinal cortex (HP-EC) samples were selected including 7 from COVID-19 patients and 7 from control donors. Multiplex immuno-histochemistry was used to detect markers of microglia and astrocytes followed by quantitative evaluation and statistical analysis. Results COVID-19 infection significantly changed density of microglia and astrocytes in HP-EC regions. It led to a decrease in quantity of neuro-protective, neurotoxic, and water-homeostasis-regulating astrocytes, while phagocytic microglia, chemotactic microglia and lipid-transporting astrocytes showed a region-specific density changes. Conclusions COVID-19 infection disrupts immune microenvironment of central nervous system, that may potentially contribute to the pathogenesis of COVID-19-related neurological symptoms as shown by changes of functional states of microglia and astrocytes.

Key words: SARS-CoV-2, microglia, astrocytes, multiplex immunohistochemistry

中图分类号:

R361.2

金忠满, 韦晖. SARS-CoV-2感染对人脑小胶质细胞和星形胶质细胞不同亚型的特异性影响[J]. 基础医学与临床, 2025, 45(7): 933-938.

JIN Zhongman, WEI Hui. Specific effects of SARS-CoV-2 infection on different subtypes of microglia and astrocytes in human brain[J]. Basic & Clinical Medicine, 2025, 45(7): 933-938.

参考文献

[1] Agyeman AA, Chin KL, Landersdorfer CB, et al. Smell and taste dysfunction in patients with COVID-19: a systematic review and meta-analysis[J]. Mayo Clin Proc, 2020, 95: 1621-1631. doi:10.1016/j.mayocp.2020.05.030.
[2] Merkler AE, Parikh NS, Mir S, et al. Risk of ischemic stroke in patients with coronavirus disease 2019 (COVID-19) vs patients with influenza[J]. JAMA Neurol, 2020, 77: 1366-1372. doi:10.1001/jamaneurol.2020.2730.
[3] Abenza Abildúa MJ, Atienza S, Carvalho Monteiro G, et al. Encephalopathy and encephalitis during acute SARS-CoV-2 infection. spanish society of neurology COVID-19 registry[J]. Neurologia, 2021, 36: 127-134. doi:10.1016/j.nrl.2020.11.013.
[4] Zhao H, Shen D, Zhou H, et al. Guillain-Barré syndrome associated with SARS-CoV-2 infection: causality or coincidence?[J]. Lancet Neurol, 2020, 19: 383-384. doi:10.1016/S1474-442230109-5.
[5] Garland EF, Hartnell IJ, Boche D. Microglia and astrocyte function and communication: What do we know in humans?[J]. Front Neurosci, 2022, 16: 824888. doi:10.3389/fnins.2022.824888.
[6] Patani R, Hardingham GE, Liddelow SA. Functional roles of reactive astrocytes in neuroinflammation and neurodegeneration[J]. Nat Rev Neurol, 2023, 19: 395-409. doi:10.1038/s41582-023-00822-1.
[7] Yang AC, Kern F, Losada PM, et al. Dysregulation of brain and choroid plexus cell types in severe COVID-19[J]. Nature, 2021, 595: 565-571. doi:10.1038/s41586-021-03710-0.
[8] Stein SR, Ramelli SC, Grazioli A, et al. SARS-CoV-2 infection and persistence in the human body and brain at autopsy[J]. Nature, 2022, 612: 758-763. doi:10.1038/s41586-022-05542-y.
[9] Qiu W, Zhang H, Bao A, et al. Standardized operational protocol for human brain banking in China[J]. Neurosci Bull, 2019, 35: 270-276. doi:10.1007/s12264-018-0306-7.
[10] World Medical Association. World medical association declaration of Helsinki: ethical principles for medical research involving human subjects[J]. JAMA, 2013, 310: 2191-2194. doi:10.1001/jama.2013.281053.
[11] Fontes-Dantas FL, Fernandes GG, Gutman EG, et al. SARS-CoV-2 spike protein induces TLR4-mediated long-term cognitive dysfunction recapitulating post-COVID-19 syndrome in mice[J]. Cell Rep, 2023, 42: 112189. doi:10.1016/j.celrep.2023.112189.
[12] Copaescu A, Smibert O, Gibson A, et al. The role of IL-6 and other mediators in the cytokine storm associated with SARS-CoV-2 infection[J]. J Allergy Clin Immunol, 2020, 146: 518-534.e1. doi:10.1016/j.jaci.2020.07.001.
[13] Zhang L, Zhou L, Bao L, et al. SARS-CoV-2 crosses the blood-brain barrier accompanied with basement membrane disruption without tight junctions alteration[J]. Signal Transduct Target Ther, 2021, 6: 1-12. doi:10.1038/s41392-021-00719-9.
[14] Villaseñor R, Kuennecke B, Ozmen L, et al. Region-specific permeability of the blood-brain barrier upon pericyte loss[J]. J Cereb Blood Flow Metab, 2017, 37: 3683-3694. doi:10.1177/0271678X17697340.
[15] Hernández VS, Zetter MA, Guerra EC, et al. ACE2 expression in rat brain: implications for COVID-19 associated neurological manifestations[J]. Exp Neurol, 2021, 345: 113837. doi:10.1016/j.expneurol.2021.113837.

SARS-CoV-2感染对人脑小胶质细胞和星形胶质细胞不同亚型的特异性影响

Specific effects of SARS-CoV-2 infection on different subtypes of microglia and astrocytes in human brain

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