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Tytuł:
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Deficiency of cGAS signaling protects against sepsis-associated encephalopathy.
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Autorzy:
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Tan C; Department of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410000, PR China.
Xu F; Department of Endocrinology and Metabolism, The Second Xiangya Hospital, Central South University, Changsha, 410000, PR China.
Xie Q; Department of Cardiology, People's Hospital of Hunan Province, Changsha, 410000, PR China.
Li F; Department of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410000, PR China. Electronic address: .
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Źródło:
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Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2021 Nov 05; Vol. 577, pp. 38-44. Date of Electronic Publication: 2021 Sep 03.
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Typ publikacji:
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Journal Article
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Język:
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English
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Imprint Name(s):
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Publication: <2002- >: San Diego, CA : Elsevier
Original Publication: New York, Academic Press.
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MeSH Terms:
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Disease Models, Animal*
Nucleotidyltransferases/*genetics
Sepsis-Associated Encephalopathy/*genetics
Signal Transduction/*genetics
Animals ; Animals, Newborn ; Astrocytes/metabolism ; Cognitive Dysfunction/genetics ; Cognitive Dysfunction/metabolism ; Cognitive Dysfunction/physiopathology ; Hippocampus/drug effects ; Hippocampus/metabolism ; Humans ; Interferon Type I/metabolism ; Male ; Maze Learning/physiology ; Mice, Inbred C57BL ; Mice, Knockout ; Microglia/metabolism ; Neurons/metabolism ; Nucleotidyltransferases/deficiency ; Protective Agents/metabolism ; Sepsis/genetics ; Sepsis/metabolism ; Sepsis/physiopathology ; Sepsis-Associated Encephalopathy/metabolism ; Mice
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Contributed Indexing:
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Keywords: Cognitive impairment; Infection; Sepsis-associated encephalopathy; Type I interferon; cGAS
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Substance Nomenclature:
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0 (Interferon Type I)
0 (Protective Agents)
EC 2.7.7.- (Nucleotidyltransferases)
EC 2.7.7.- (cGAS protein, mouse)
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Entry Date(s):
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Date Created: 20210910 Date Completed: 20211126 Latest Revision: 20240226
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Update Code:
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20240226
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DOI:
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10.1016/j.bbrc.2021.09.003
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PMID:
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34507063
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Sepsis is a life-threatening inflammatory syndrome secondary to infection. Thanks to the advances of antibiotics and life-supporting techniques, the mortality of sepsis has been decreasing in recent decades. Nevertheless, sepsis-associated encephalopathy (SAE) is still common in septic patients, which promotes the mortality of septic patients and results in cognitive dysfunction in survivors. Full understanding and effective medicine in the treatment of SAE is currently scant. Here, we revealed a novel role of cGAS signaling in the pathogenesis of SAE. Deficiency of cGas significantly restored cognitive impairment in sepsis mice model. The restoration may attribute to the recovery of neo-neuron decline that associated with the decrease of activated microglia and astrocytes in the hippocampus of cGas-deficient mice. In addition, type I interferon (IFN) signaling, a downstream of cGAS pathway, was boosted in the hippocampus of septic mice, which was dramatically attenuated by deleting cGas. Moreover, administration of recombinant IFNβ markedly reversed the protection of ablation of cGas in the cognitive impairment in sepsis. Collectively, cGAS promotes the pathogenesis of SAE by up-regulating type I IFN signaling. Blocking cGAS may be a promising strategy for preventing encephalopathy in sepsis.
Competing Interests: Declaration of competing interest The authors declare no conflict of interests in the present study.
(Copyright © 2021 Elsevier Inc. All rights reserved.)