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M1-Type Microglia-Derived Extracellular Vesicles Overexpressing IL-1R1 Promote Postoperative Cognitive Dysfunction by Regulating Neuronal Inflammation

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Abstract

Postoperative cognitive dysfunction (POCD) is a common complication after surgical anesthesia, mainly manifested as memory impairment, decreased attention, and cognitive function with mood and personality changes. Activated microglia (M1-type microglia) have been demonstrated to release inflammatory substances (IL-1β, TNF-α, etc.) that cause neuronal degeneration and death by activating the NF-κB signaling pathway and upregulating Caspase-3 and Bax. However, the pathogenesis of POCD is still not fully understood and needs further research. In the present study, we investigated the effect of M1-type microglia-derived extracellular vesicles (EVsM1−Microglia) in the pathological process of POCD. The levels of NF-κB phosphorylation and IL-1β protein expression in hippocampal neurons were significantly increased in the Surgery group, while PSD95 and MAP2 were significantly decreased. Surgery induced microglia activation, synapse-associated protein decrease, and neuronal degeneration in hippocampus. And the amount of spine and mushroom spine significantly decreased in surgical mice, which was reverted in the presence of IL-1R1 siRNA. In addition, EVsM1−Microglia promoted synaptic loss and neuron degeneration independent of surgery and microglia activation. Furthermore, EVsM1−Microglia promoted memory defects in surgical mice. We demonstrated that EVsM1−Microglia with high expression of IL-1R1 promote POCD development by regulating neuronal inflammation.

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Data and materials relevant to the study are available from the corresponding author upon reasonable request.

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Funding

This study was supported by the National Natural Science Foundation of China (81971020).

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Authors and Affiliations

  1. Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe Dong Road, Zhengzhou, 450000, People’s Republic of China

    Zheng Qi, Yang Yu, Bin Cao, Hua Shao & Jian-Jun Yang

  2. Henan Province International Joint Laboratory of Pain, Cognition and Emotion, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe Dong Road, Zhengzhou, 450000, People’s Republic of China

    Zheng Qi, Yang Yu, Bin Cao, Hua Shao & Jian-Jun Yang

  3. Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, People’s Republic of China

    Yu Su

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  1. Zheng Qi
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Contributions

ZQ contributed to sample collection, designed the methods, designed experiments design, and performed validation, formal analysis, investigation, data curation, and writing (original draft, review, and editing); YY and YS designed the methods, isolated EVs, and performed NTA analysis; BC and HS: western blot and animal experiments; JJY: conceptualization, writing (review and editing), project administration, and funding acquisition. All the authors have proofread the final version of the manuscript.

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Correspondence to Jian-Jun Yang.

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Qi, Z., Yu, Y., Su, Y. et al. M1-Type Microglia-Derived Extracellular Vesicles Overexpressing IL-1R1 Promote Postoperative Cognitive Dysfunction by Regulating Neuronal Inflammation. Inflammation 46, 2254–2269 (2023). https://doi.org/10.1007/s10753-023-01875-6

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  • DOI: https://doi.org/10.1007/s10753-023-01875-6

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