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M1-Type Microglia-Derived Extracellular Vesicles Overexpressing IL-1R1 Promote Postoperative Cognitive Dysfunction by
Zheng Qi1,2, Yang Yu1,2, Yu Su3
1Department 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.
Inflammation
|July 28, 2023
Summary
Extracellular vesicles from activated M1-type microglia worsen postoperative cognitive dysfunction (POCD) by promoting neuronal inflammation and memory deficits. These EVs contribute to synaptic loss and neuron degeneration, highlighting a novel mechanism in POCD development.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Postoperative cognitive dysfunction (POCD) is a common complication following surgery and anesthesia, characterized by memory impairment and cognitive decline.
- Activated microglia, particularly M1-type, release inflammatory factors that can lead to neuronal damage via pathways like NF-κB signaling.
- The precise mechanisms underlying POCD pathogenesis remain incompletely understood, necessitating further investigation into cellular and molecular contributors.
Purpose of the Study:
- To investigate the role of extracellular vesicles derived from M1-type microglia (EVsM1-Microglia) in the pathological processes of POCD.
- To elucidate the impact of EVsM1-Microglia on synaptic integrity, neuronal degeneration, and cognitive function in a surgical mouse model.
Main Methods:
- Surgical procedures were performed on mice to induce POCD.
- Levels of NF-κB phosphorylation, IL-1β, PSD95, and MAP2 were measured in hippocampal neurons.
- Microglia activation, synaptic structures, and the effects of EVsM1-Microglia (with and without IL-1R1 siRNA) on neuronal health and memory were assessed.
Main Results:
- Surgery significantly increased NF-κB phosphorylation and IL-1β, while decreasing PSD95 and MAP2 in hippocampal neurons, indicating neuronal damage and inflammation.
- Surgery induced microglia activation, reduced synaptic density, and caused neuronal degeneration, effects partially mitigated by IL-1R1 siRNA.
- EVsM1-Microglia exacerbated synaptic loss, neuron degeneration, and memory deficits in surgical mice, independent of surgery or microglia activation itself.
Conclusions:
- M1-type microglia-derived extracellular vesicles (EVsM1-Microglia) play a significant role in promoting POCD development.
- EVsM1-Microglia, particularly those with high IL-1R1 expression, contribute to POCD by inducing neuronal inflammation, synaptic loss, and cognitive impairment.
- Targeting EVsM1-Microglia or their inflammatory signaling pathways presents a potential therapeutic strategy for mitigating POCD.
