AUTHOR=Li Yu-Ning , Liang Ya-Ping , Zhang Jing-Qian , Li Na , Wei Zhi-Yuan , Rao Yijian , Chen Jian-Huan , Jin Yun-Yun 

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

JOURNAL=Frontiers in Neuroscience

VOLUME=18

YEAR=2024

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2024.1435185

DOI=10.3389/fnins.2024.1435185

ISSN=1662-453X

ABSTRACT=<sec><title>Introduction</title><p>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.</p></sec><sec><title>Methods</title><p>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.</p></sec><sec><title>Results</title><p>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 (<italic>Azin1</italic>) and editing events in lincRNAs such as maternally expressed gene 3 (<italic>Meg3</italic>), <italic>AW112010</italic>, and macrophage M2 polarization regulator (<italic>Mm2pr</italic>). Importantly, geranylgeranyl diphosphate synthase 1 (<italic>Ggps1</italic>) 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 (<italic>Gch1</italic>) and non-coding RNA activated by DNA damage (<italic>Norad</italic>), both with the editing level positively correlated with both post-LPS treatment time and edited gene expression in cerebral vessels and CECs.</p></sec><sec><title>Discussion</title><p>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.</p></sec>