Author:
Liu Chong,Zhao Xue-Min,Wang Qiao,Du Ting-Ting,Zhang Mo-Xuan,Wang Hui-Zhi,Li Ren-Peng,Liang Kun,Gao Yuan,Zhou Si-Yu,Xue Tao,Zhang Jian-Guo,Han Chun-Lei,Shi Lin,Zhang Liang-Wen,Meng Fan-Gang
Abstract
AbstractImpaired activation and regulation of the extinction of inflammatory cells and molecules in injured neuronal tissues are key factors in the development of epilepsy. SerpinA3N is mainly associated with the acute phase response and inflammatory response. In our current study, transcriptomics analysis, proteomics analysis, and Western blotting showed that the expression level of Serpin clade A member 3N (SerpinA3N) is significantly increased in the hippocampus of mice with kainic acid (KA)-induced temporal lobe epilepsy, and this molecule is mainly expressed in astrocytes. Notably, in vivo studies using gain- and loss-of-function approaches revealed that SerpinA3N in astrocytes promoted the release of proinflammatory factors and aggravated seizures. Mechanistically, RNA sequencing and Western blotting showed that SerpinA3N promoted KA-induced neuroinflammation by activating the NF-κB signaling pathway. In addition, co-immunoprecipitation revealed that SerpinA3N interacts with ryanodine receptor type 2 (RYR2) and promotes RYR2 phosphorylation. Overall, our study reveals a novel SerpinA3N-mediated mechanism in seizure-induced neuroinflammation and provides a new target for developing neuroinflammation-based strategies to reduce seizure-induced brain injury.
Funder
2021 Reform Development of Beijing Neurosurgical Institute
National Natural Science Foundation of China
Beijing Natural Science Foundation Program, Scientific Research Key Program of Beijing Municipal Commission of Education
Publisher
Springer Science and Business Media LLC
Subject
Cellular and Molecular Neuroscience,Neurology,Immunology,General Neuroscience
Cited by
3 articles.
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