Jin Yun-Yun, Liang Ya-Ping, Wei Zhi-Yuan, Sui Wei-Jia, Chen Jian-Huan
Laboratory of Genomic and Precision Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu 214122, China.
Joint Primate Research Center for Chronic Diseases, Jiangnan University and Institute of Zoology, Guangdong Academy of Sciences, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu 214122, China.
Brain Commun. 2024 Aug 8;6(4):fcae260. doi: 10.1093/braincomms/fcae260. eCollection 2024.
Sepsis-associated encephalopathy is a diffuse brain dysfunction secondary to infection. It has been established that factors such as age and sex can significantly contribute to the development of sepsis-associated encephalopathy. Our recent study implicated a possible link between adenosine-to-inosine RNA editing and sepsis-associated encephalopathy, yet the dynamics of adenosine-to-inosine RNA editing during sepsis-associated encephalopathy and how it could be influenced by factors such as age, sex and antidepressants remain uninvestigated. Our current study analysed and validated transcriptome-wide changes in adenosine-to-inosine RNA editing in the hippocampus of different septic mouse models. Seventy-four sites in 64 genes showed significant differential RNA editing over time in septic mice induced by caecal ligation and perforation. The differential RNA editing might contribute to the RNA expression regulation of the edited genes, with 42.2% differentially expressed. These differentially edited genes, especially those with missense editing, such as glutamate receptor, ionotropic, kainate 2 (, p.M620V), filamin A (, p.S2331G) and capicua transcriptional repressor (, p.E2270G), were mainly involved in abnormal social behaviour and neurodevelopmental and psychiatric disorders. Significant effects of age and sex were also observed on sepsis-associated RNA editing. Further comparison highlighted 40 common differential RNA editing sites that caecal ligation and perforation-induced and lipopolysaccharide-induced septic mouse models shared. Interestingly, these findings demonstrate temporal dynamics of adenosine-to-inosine RNA editing in the mouse hippocampus during sepsis, add to the understanding of age and sex differences in the disease and underscore the role of the epigenetic process in sepsis-associated encephalopathy.
脓毒症相关性脑病是继发于感染的弥漫性脑功能障碍。已经确定年龄和性别等因素可显著促成脓毒症相关性脑病的发生。我们最近的研究表明腺苷到次黄苷RNA编辑与脓毒症相关性脑病之间可能存在联系，但脓毒症相关性脑病期间腺苷到次黄苷RNA编辑的动态变化以及它如何受到年龄、性别和抗抑郁药等因素的影响仍未得到研究。我们目前的研究分析并验证了不同脓毒症小鼠模型海马中腺苷到次黄苷RNA编辑的全转录组变化。在盲肠结扎和穿孔诱导的脓毒症小鼠中，64个基因中的74个位点随时间显示出显著的差异RNA编辑。差异RNA编辑可能有助于编辑基因的RNA表达调控，其中42.2%差异表达。这些差异编辑的基因，尤其是那些有错义编辑的基因，如离子型红藻氨酸受体2（，p.M620V）、细丝蛋白A（，p.S2331G）和capicua转录抑制因子（，p.E2270G），主要参与异常社会行为以及神经发育和精神疾病。年龄和性别对脓毒症相关性RNA编辑也有显著影响。进一步比较突出了盲肠结扎和穿孔诱导的脓毒症小鼠模型与脂多糖诱导的脓毒症小鼠模型共有的40个常见差异RNA编辑位点。有趣的是，这些发现揭示了脓毒症期间小鼠海马中腺苷到次黄苷RNA编辑的时间动态变化，增进了对该疾病年龄和性别差异的理解，并强调了表观遗传过程在脓毒症相关性脑病中的作用。
