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Interleukin-33 ameliorates perioperative neurocognitive disorders by modulating microglial state.
Yang, Di; Sun, Yi; Lin, Dandan; Li, Sijie; Zhang, Yan; Wu, Anshi; Wei, Changwei.
Afiliación
  • Yang D; Department of Anesthesiology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
  • Sun Y; Department of Anesthesiology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
  • Lin D; Department of Anesthesiology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
  • Li S; Department of Anesthesiology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
  • Zhang Y; State Key Laboratory of Membrane Biology, College of Life Sciences, Peking University, Beijing, China. Electronic address: yanzhang@pku.edu.cn.
  • Wu A; Department of Anesthesiology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China. Electronic address: wuanshi1965@163.com.
  • Wei C; Department of Anesthesiology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China. Electronic address: changwei.wei@ccmu.edu.cn.
Neuropharmacology ; 253: 109982, 2024 Aug 01.
Article en En | MEDLINE | ID: mdl-38701943
ABSTRACT
Perioperative neurocognitive disorders (PND) are cognitive dysfunctions that usually occur in elderly patients after anesthesia and surgery. Microglial overactivation is a key underlying mechanism. Interleukin-33 (IL-33) is a member of the IL-1 family that orchestrates microglial function. In the present study, we explored how IL-33, which regulates microglia, contributes to cognitive improvement in a male mouse model of PND. An exploratory laparotomy was performed to establish a PND model. The expression levels of IL-33 and its receptor ST2 were evaluated using Western blot. IL-33/ST2 secretion, microglial density, morphology, phagocytosis of synapse, and proliferation, and dystrophic microglia were assessed using immunofluorescence. Synaptic plasticity was measured using Golgi staining and long-term potentiation. The Morris water maze and open field test were used to evaluate cognitive function and anxiety. Hippocampal expression of IL-33 and ST2 were elevated on postoperative day 3. We confirmed that IL-33 was secreted by astrocytes and neurons, whereas ST2 mainly colocalized with microglia. IL-33 treatment induced microgliosis after anesthesia and surgery. These microglia had larger soma sizes and shorter and fragmented branches. Compared to the Surgery group, IL-33 treatment reduced the synaptic phagocytosis of microglia and increased microglial proliferation and dystrophic microglia. IL-33 treatment also reversed the impaired synaptic plasticity and cognitive function caused by anesthesia and surgery. In conclusion, these results indicate that IL-33 plays a key role in regulating microglial state and synaptic phagocytosis in a PND mouse model. IL-33 treatment has a therapeutic potential for improving cognitive dysfunction in PND.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Microglía / Interleucina-33 / Ratones Endogámicos C57BL Límite: Animals Idioma: En Revista: Neuropharmacology Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Microglía / Interleucina-33 / Ratones Endogámicos C57BL Límite: Animals Idioma: En Revista: Neuropharmacology Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido