Sepsis-associated encephalopathy (SAE) is a common complication of sepsis, which is a life-threatening condition resulting from a dysregulated host response to infection. Pyroptosis, a pro-inflammatory mode of lytic cell death mediated by GSDMD (Gasdermin D), is involved in the pathogenesis of SAE. While autophagy has been extensively studied in SAE, the role of nuclear autophagy is not yet well understood. In this study, we aimed to investigate the involvement of pyroptosis and neural nuclear autophagy in the pathogenesis of SAE. We analyzed a CLP (cecal ligation and puncture)-induced SAE model in wild-type and GSDMD(-/-) mice to gain insights into the underlying mechanisms. Here, we show that in sepsis, neural nuclear autophagy is extremely activated, and nuclear LaminB decreases and is accompanied by an increase in the ratio of LC3BII/I. These effects can be reversed in GSDMD(-/-) mice. The behavioral outcomes of septic wild-type mice are impaired by the evidence from the novel object recognition test (NORT) and open field test (OFT), but are improved in septic GSDMD(-/-) mice. In conclusion, our study demonstrates the activation of neural nuclear autophagy in SAE. The absence of GSDMD inhibits nuclear autophagy and improves the behavioral outcomes of SAE.
基金：
National Natural Science Foundation of China [81801072, 82000088]
第一作者单位：[1]Huazhong Univ Sci & Technol,Tongji Hosp,Tongji Med Coll,Trauma Ctr,Dept Emergency & Trauma Surg,Wuhan 430030,Peoples R China
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Su Wei,Xie Zhenxing,Bai Xiangjun,et al.The Absence of Gasdermin D Reduces Nuclear Autophagy in a Cecal Ligation and Puncture-Induced Sepsis-Associated Encephalopathy Mouse Model[J].BRAIN SCIENCES.2023,13(3):doi:10.3390/brainsci13030478.
APA：
Su, Wei,Xie, Zhenxing,Bai, Xiangjun,Li, Zhanfei&Liu, Xinghua.(2023).The Absence of Gasdermin D Reduces Nuclear Autophagy in a Cecal Ligation and Puncture-Induced Sepsis-Associated Encephalopathy Mouse Model.BRAIN SCIENCES,13,(3)
MLA：
Su, Wei,et al."The Absence of Gasdermin D Reduces Nuclear Autophagy in a Cecal Ligation and Puncture-Induced Sepsis-Associated Encephalopathy Mouse Model".BRAIN SCIENCES 13..3(2023)
