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Effect of Oxygen–Glucose Deprivation of Microglia-Derived Exosomes on Hippocampal Neurons: A Study on miR-124 and Inflammatory Cytokines

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Abstract

Stroke is a cerebrovascular disease that threatens human health. Developing safe and effective drugs and finding therapeutic targets has become an urgent scientific problem. The aim of this study was to investigate the effect of oxygen–glucose deprivation of the microglia-derived exosome on hippocampal neurons and its relationship to miR-124 in the exosome. We incubated hippocampal neurons with exosomes secreted by oxygen–glucose deprivation/ reoxygenation (OGD/R) microglia. The levels of glutamic acid (GLU) and gamma-aminobutyric acid (GABA) in the culture supernatant were detected by ELISA. CCK-8 was used to measure neuronal survival rates. The mRNA levels of TNF-α and IL-6 were detected by RT-qPCR to evaluate the effect of exosomes on neurons. RT-qPCR was then used to detect miR-124 in microglia and their secreted exosomes. Finally, potential targets of miR-124 were analyzed through database retrieval, gene detection with dual luciferase reporters, and western blotting experiments. The results showed that the contents of GLU, TNF-α and IL-6 mRNA increased in the supernatant of cultured hippocampal neurons, the content of GABA decreased, and the survival rate of neurons decreased. Oxygen–glucose deprivation increases miR-124 levels in microglia and their released exosomes. miR-124 acts as a target gene on cytokine signaling suppressor molecule 1(SOCS1), while miR-124 inhibitors reduce the expression of TNF-α and IL-6 mRNA in neurons. These results suggest that oxygen- and glucose-deprived microglia regulate inflammatory cytokines leading to reduced neuronal survival, which may be achieved by miR-124 using SOCS1 as a potential target.

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Acknowledgements

This work was supported by the Natural Science Foundation of China (81660243), Guizhou Provincial Science and Technology Projects (Qiankehejichu -ZK-[2021, 2023] yiban 415, 323). And Science Innovation 2030–Brain Science and BrainInspired Intelligence Technology Major Project (2021ZD0201100, 2021ZD0201103); Department of Education of Guizhou Province(Guizhou Teaching and Technology [2023]015) .

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Author notes

  1. Yizhen Zhu, Xue Zhao and Ruojing Liu These authors contributed equally to this work.

Authors and Affiliations

  1. Class 5, Grade 2023, Clinical Medicine, Guizhou Medical University, Gui’an New District, Guizhou, 561113, People’s Republic of China

    Yizhen Zhu

  2. Department of Human Anatomy, Guizhou Medical University School of Basic Medicine, Gui’an New District, Guizhou, 561113, People’s Republic of China

    Xue Zhao, Ruojing Liu, Dan Yang & Guo Ge

  3. Key Laboratory of Human Brain Bank for Functions and Diseases of Department of Education of Guizhou Province, Guizhou Medical University School of Basic Medicine, Guizhou, 561113, People’s Republic of China

    Dan Yang & Guo Ge

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  1. Yizhen Zhu
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Contributions

Yizhen ZHU and Guo GE conceived the research; Xue ZHAO, Baofei SUN, and Dan YANG performed the experiments; Xue ZHAO analyzed the data; Dan YANG, and Ruojing LIU contributed reagents/materials /analysis tools; Yizhen ZHU wrote the paper. All authors contributed to the discussion and revision of the manuscript.

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Correspondence to Guo Ge.

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Zhu, Y., Zhao, X., Liu, R. et al. Effect of Oxygen–Glucose Deprivation of Microglia-Derived Exosomes on Hippocampal Neurons: A Study on miR-124 and Inflammatory Cytokines. J Mol Histol (2024). https://doi.org/10.1007/s10735-024-10193-6

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