Dynamic A-to-I RNA editing during acute neuroinflammation in sepsis-associated encephalopathy.

Introduction: The activation of cerebral endothelial cells (CECs) has recently been reported to be the earliest acute neuroinflammation event in the CNS during sepsis-associated encephalopathy (SAE). Importantly, adenosine-to-inosine (A-to-I) RNA editing mediated by ADARs has been associated with SAE, yet its role in acute neuroinflammation in SAE remains unclear.
Methods: Our current study systematically analyzed A-to-I RNA editing in cerebral vessels, cerebral endothelial cells (CECs), and microglia sampled during acute neuroinflammation after treatment in a lipopolysaccharide (LPS)-induced SAE mouse model.
Results: Our results showed dynamic A-to-I RNA editing activity changes in cerebral vessels during acute neuroinflammation. Differential A-to-I RNA editing (DRE) associated with acute neuroinflammation were identified in these tissue or cells, especially missense editing events such as S367G in antizyme inhibitor 1 ( Azin1 ) and editing events in lincRNAs such as maternally expressed gene 3 ( Meg3 ), AW112010 , and macrophage M2 polarization regulator ( Mm2pr ). Importantly, geranylgeranyl diphosphate synthase 1 ( Ggps1 ) and another three genes were differentially edited across cerebral vessels, CECs, and microglia. Notably, Spearman correlation analysis also revealed dramatic time-dependent DRE during acute neuroinflammation, especially in GTP cyclohydrolase1 ( Gch1 ) and non-coding RNA activated by DNA damage ( Norad ), both with the editing level positively correlated with both post-LPS treatment time and edited gene expression in cerebral vessels and CECs.
Discussion: The findings in our current study demonstrate substantial A-to-I RNA editing changes during acute neuroinflammation in SAE, underlining its potential role in the disease.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer QL declared a past co-authorship with the author J-HC to the handling editor. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
(Copyright © 2024 Li, Liang, Zhang, Li, Wei, Rao, Chen and Jin.)