Hydrogen sulfide ameliorates lipopolysaccharide-induced anxiety-like behavior by inhibiting checkpoint kinase 1 activation in the hippocampus of mice

doi:10.1016/j.expneurol.2023.114586

科研成果详情

题名	Hydrogen sulfide ameliorates lipopolysaccharide-induced anxiety-like behavior by inhibiting checkpoint kinase 1 activation in the hippocampus of mice
作者	Shentu, Yangping 1; Chen, Mengfan2; Wang, Hui 3; Du, Xiaotong2,4; Zhang, Wenjing 5; Xie, Guizhen3; Zhou, Shaoyan3; Ding, Lu 3; Zhu, Yun1; Zhu, Min3; Zhang, Nan3; Du, Congkuo3; Ma, Jianshe3; Chen, Ran3; Yang, Jinge 6; Fan, Xiaofang3; Gong, Yongsheng3; Zhang, Hongyu2,4; Fan, Junming3,4
发表日期	2023-10-26
发表期刊	Experimental neurology 影响因子和分区
语种	英语
原始文献类型	Journal Article ; Article
关键词	Anxiety-like behavior CSE Chk1 H(2)S Hippocampus Inflammasome H2S
其他关键词	NLRP3 INFLAMMASOME ACTIVATION ; DEPRESSIVE-LIKE BEHAVIOR ; NF-KAPPA-B ; CELL-CYCLE ; CONTRIBUTES ; INVOLVEMENT ; PATHWAY
摘要	Hydrogen sulfide (H2S), an endogenous gasotransmitter, exhibits the anxiolytic roles through its anti-inflammatory effects, although its underlying mechanisms remain largely elusive. Emerging evidence has documented that cell cycle checkpoint kinase 1 (Chk1)-regulated DNA damage plays an important role in the neurodegenerative diseases; however, there are few relevant reports on the research of Chk1 in neuropsychiatric diseases. Here, we aimed to investigate the regulatory role of H2S on Chk1 in lipopolysaccharide (LPS)-induced anxiety-like behavior focusing on inflammasome activation in the hippocampus. Cystathionine γ-lyase (CSE, a H2S-producing enzyme) knockout (CSE-/-) mice displayed anxiety-like behavior and activation of inflammasome-mediated inflammatory responses, manifesting by the increase levels of interleukin-1β (IL-1β), IL-6, and ionized calcium-binding adaptor molecule-1 (Iba-1, microglia marker) expression in the hippocampus. Importantly, expression of p-Chk1 and γ-H2AX (DNA damage marker) levels were also increased in the hippocampus of CSE-/- mice. LPS treatment decreased the expression of CSE and CBS while increased p-Chk1 and γ-H2AX levels and inflammasome-activated neuroinflammation in the hippocampus of mice. Moreover, p-Chk1 and γ-H2AX protein levels and cellular immunoactivity were significantly increased while CSE and CBS were markedly decreased in cultured BV2 cells followed by LPS treatment. Treatment of mice with GYY4137, a donor of H2S, inhibited LPS-induced increased in p-Chk1 and γ-H2AX levels, mitigated inflammasome activation and inflammatory responses as well as amelioration of anxiety-like behavior. Notably, SB-218078, a selective Chk1 inhibitor treatment attenuated the effect of LPS on inflammasome activation and inflammatory responses and the induction of anxiety-like behavior. Finally, STAT3 knockdown with AAV-STAT3 shRNA alleviated LPS-induced anxiety-like behavior and inhibited inflammasome activation in the hippocampus, and blockade of NLRP3 with MCC950 attenuated neuroinflammation induction and ameliorated LPS-induced anxiety-like behavior. Overall, this study indicates that downregulation of Chk1 activity by H2S activation may be considered as a valid strategy for preventing the progression of LPS-induced anxiety-like behavior
资助项目	Ningbo Natural Science Foundation of China [2021J030]; Project of National College Student Innovation and Entrepreneurship Training Program [202210343037]; Foundation of Zhejiang Educational Committee [Y202044729]; Foundation of Jiangxi Educa- tional Committee [GJJ2205806]
出版者	ACADEMIC PRESS INC ELSEVIER SCIENCE
ISSN	0014-4886
EISSN	1090-2430
卷号	371
DOI	10.1016/j.expneurol.2023.114586
页数	13
WOS类目	Neurosciences
WOS研究方向	Neurosciences & Neurology
WOS记录号	WOS:001106133100001
收录类别	PUBMED ; SCIE ; SCOPUS
URL	查看原文
PubMed ID	37898396
SCOPUSEID	2-s2.0-85175234235
通讯作者地址	[Zhang, Hongyu]Institute of Cixi Biomedical Research,Wenzhou Medical University,Zhejiang,Cixi,315302,China ; [Gong, Yongsheng]Institute of Hypoxia Medicine,School of Basic Medical Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,325035,China
Scopus学科分类	Neurology;Developmental Neuroscience
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/183712
专题	附属第一医院基础医学院（机能实验教学中心）药学院（分析测试中心）仁济学院
通讯作者	Gong, Yongsheng; Zhang, Hongyu
作者单位	1.Department of Pathology,The First Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325000,China; 2.School of Pharmaceutical Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,325035,China; 3.Institute of Hypoxia Medicine,School of Basic Medical Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,325035,China; 4.Institute of Cixi Biomedical Research,Wenzhou Medical University,Zhejiang,Cixi,315302,China; 5.Renji College,Wenzhou Medical University,Zhejiang,Wenzhou,325035,China; 6.Department of Medical Technology,Jiangxi Medical College,Jiangxi,Shangrao,334709,China
第一作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院
通讯作者单位	温州医科大学; 基础医学院（机能实验教学中心）
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Shentu, Yangping,Chen, Mengfan,Wang, Hui,et al. Hydrogen sulfide ameliorates lipopolysaccharide-induced anxiety-like behavior by inhibiting checkpoint kinase 1 activation in the hippocampus of mice[J]. Experimental neurology,2023,371.
APA	Shentu, Yangping., Chen, Mengfan., Wang, Hui., Du, Xiaotong., Zhang, Wenjing., ... & Fan, Junming. (2023). Hydrogen sulfide ameliorates lipopolysaccharide-induced anxiety-like behavior by inhibiting checkpoint kinase 1 activation in the hippocampus of mice. Experimental neurology, 371.
MLA	Shentu, Yangping,et al."Hydrogen sulfide ameliorates lipopolysaccharide-induced anxiety-like behavior by inhibiting checkpoint kinase 1 activation in the hippocampus of mice".Experimental neurology 371(2023).