Microglial pyroptosis induced by SENP7 via the cGAS/STING/IRF3 pathway contributes to neuronal apoptosis.

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Tác giả: Ke Hua, Lin Liu, Fei Xiao, Jinyue Yang, Hanqing Yao

Ngôn ngữ: eng

Ký hiệu phân loại:

Thông tin xuất bản: England : Cytokine , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 717590

BACKGROUND: Maternal anesthetic exposure may exacerbate significant neurocognitive risks in the immature brains of fetuses. However, the mechanisms through which sevoflurane exposure during pregnancy results in cognitive impairments in offspring remain unclear. METHODS: Pregnant C57BL/6 mice (gestational day 14) were intervented with 2.5 % sevoflurane for 6 h. Morris water maze test and context fear conditioning test were utilized to evaluate the cognitive function of the offspring. BV2 cells were stimulated with LPS-ATP to evaluate the impacts of SENP7 on microglial pyroptosis. A co-culture experiment was conducted to investigate the apoptosis of mouse hippocampal neuronal cells induced by BV2 cells. The regulatory roles of SENP7 in the cGAS/STING/IRF3 pathway were assessed using an immunoprecipitation SUMOylation assay, along with Western blot analysis. RESULTS: Sevoflurane exposure during pregnancy resulted in cognitive impairments in offspring mice, which were associated with the upregulation of SENP7, Iba1, Caspase1, and GSDMD-N proteins, as well as the downregulation of NeuN and TH proteins in the brains of the offspring. The knockdown of SENP7 inhibited the elevation of GSDMD-N, Caspase1, and NLRP3 protein levels, subsequently reducing the concentrations of IL-1β and IL-18 in BV2 cells induced by LPS-ATP. Furthermore, SENP7 facilitated the activation of the cGAS/STING/IRF3 axis by regulating the deSUMOylation of cGAS, which triggered microglial pyroptosis and subsequently led to neuronal apoptosis. CONCLUSION: Maternal exposure to sevoflurane increased the expression of SENP7 in the brains of offspring and resulted in detrimental effects on cognitive function. This phenomenon was associated with neuronal apoptosis triggered by microglial pyroptosis, which was regulated by SENP7 through the cGAS/STING/IRF3 pathway.
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