Academic Journal
The role of astrocytic GSDME in Sepsis-associated cognitive dysfunction.
| Τίτλος: | The role of astrocytic GSDME in Sepsis-associated cognitive dysfunction. |
|---|---|
| Συγγραφείς: | Zhao X; Department of Integrative Medicine and Neurobiology, School of Basic Medical Science, State Key Laboratory of Brain Function and Disorders and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200032, China; Department of traditional Chinese medicine, Zhangye People's Hospital affiliated to Hexi University, Zhangye 734000, China., Wu X; Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Department of Anesthesiology, Shanghai Geriatric Medical Center, Shanghai 201104, China; Shanghai Key laboratory of Perioperative Stress and Protection, Shanghai 200032, China., Sun Q; Department of Integrative Medicine and Neurobiology, School of Basic Medical Science, State Key Laboratory of Brain Function and Disorders and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200032, China., Ma B; Department of Integrative Medicine and Neurobiology, School of Basic Medical Science, State Key Laboratory of Brain Function and Disorders and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200032, China., Zhang T; Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Department of Anesthesiology, Shanghai Geriatric Medical Center, Shanghai 201104, China; Shanghai Key laboratory of Perioperative Stress and Protection, Shanghai 200032, China., Wang D; Department of Integrative Medicine and Neurobiology, School of Basic Medical Science, State Key Laboratory of Brain Function and Disorders and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200032, China., Gao S; Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Department of Anesthesiology, Shanghai Geriatric Medical Center, Shanghai 201104, China; Shanghai Key laboratory of Perioperative Stress and Protection, Shanghai 200032, China., Jiang Y; Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Department of Anesthesiology, Shanghai Geriatric Medical Center, Shanghai 201104, China; Shanghai Key laboratory of Perioperative Stress and Protection, Shanghai 200032, China., Shen R; Shanghai Laboratory Animal Research Center, Shanghai 201203, China. Electronic address: shenruling@slarc.org.cn., Chen W; Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Department of Anesthesiology, Shanghai Geriatric Medical Center, Shanghai 201104, China; Shanghai Key laboratory of Perioperative Stress and Protection, Shanghai 200032, China. Electronic address: chenwank@163.com., Wang J; Department of Integrative Medicine and Neurobiology, School of Basic Medical Science, State Key Laboratory of Brain Function and Disorders and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200032, China. Electronic address: jwangf@shmu.edu.cn. |
| Πηγή: | International immunopharmacology [Int Immunopharmacol] 2026 Jul 15; Vol. 181, pp. 116736. Date of Electronic Publication: 2026 Apr 28. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 100965259 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-1705 (Electronic) Linking ISSN: 15675769 NLM ISO Abbreviation: Int Immunopharmacol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Amsterdam ; New York : Elsevier Science, c2001- |
| Ιατρικοί όροι (MeSH): | Astrocytes*/metabolism , Astrocytes*/drug effects , Cognitive Dysfunction*/drug therapy , Cognitive Dysfunction*/etiology , Cognitive Dysfunction*/metabolism , Iridoids*/pharmacology , Iridoids*/therapeutic use , Sepsis*/complications , Sepsis*/drug therapy , Sepsis-Associated Encephalopathy*/drug therapy , Sepsis-Associated Encephalopathy*/metabolism, Hippocampus/drug effects ; Hippocampus/metabolism ; Hippocampus/pathology ; Pyroptosis/drug effects ; Animals ; Male ; Mice ; Mice, Inbred C57BL ; Disease Models, Animal ; Humans |
| Περίληψη: | Sepsis-associated encephalopathy (SAE) is a neurofunctional disorder resulting from sepsis, primarily manifested as acute brain dysfunction and long-term cognitive decline. This study utilizes the cecal ligation and puncture (CLP) model to investigate the role of Gasdermin E (GSDME)-mediated pyroptosis in hippocampal astrocytes in the pathogenesis of SAE-related cognitive dysfunction, as well as the therapeutic potential of geniposide, an active compound from the traditional Chinese medicine formula An-gong Niu-huang pill (Ag-NhP). Our results demonstrate that CLP significantly upregulates GSDME expression and cleavage in hippocampal astrocytes, which contributes to cognitive dysfunction in mice. Notably, astrocyte-specific knockdown of GSDME markedly alleviates cognitive impairment in septic mice, highlighting the critical role of GSDME-mediated pyroptosis in SAE. Further, we identified geniposide as an active component of Ag-NhP that inhibits GSDME-mediated pyroptosis. Geniposide not only inhibits GSDME activation but also prevents the translocation of cleaved GSDME to the cell membrane. In vivo, geniposide administration significantly improves cognitive dysfunction induced by SAE. In conclusion, our findings reveal that GSDME-mediated astrocytic pyroptosis in the hippocampus plays a pivotal role in the development of cognitive dysfunction, and that geniposide effectively inhibits this process, offering potential therapeutic benefits for SAE-induced cognitive impairment. (Copyright © 2024. Published by Elsevier B.V.) |
| Competing Interests: | Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: Cognitive dysfunction; GSDME; Geniposide; Sepsis-associated encephalopathy |
| Substance Nomenclature: | 145295QLXY (geniposide) 0 (Iridoids) |
| Entry Date(s): | Date Created: 20260429 Date Completed: 20260715 Latest Revision: 20260715 |
| Update Code: | 20260716 |
| DOI: | 10.1016/j.intimp.2026.116736 |
| PMID: | 42055495 |
| Βάση Δεδομένων: | MEDLINE |
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