Key miRNAs associated with memory and learning disorder upon exposure to sevoflurane determined by RNA sequencing.

Abstract

The study aimed to identify differentially expressed microRNAs (miRNAs/miRs) and explore the mechanisms governing impaired memory and learning ability in developing brains exposed to sevoflurane. A total of six 7-day-old male ICR mice were randomly assigned into the sevoflurane anesthesia group (treated with 2.4% sevoflurane) or control group (treated with normal saline solution at the same dose). After 14 days, the mice were subjected to a Morris water maze experiment. Then, the animals were sacrificed and hippocampus tissues were isolated. RNAs in hippocampus tissues were sequenced and the differential miRNA expression profiles were identified by a bioinformatics approach. The learning and memory function of mice were significantly affected by sevoflurane exposure. A total of 18 miRNAs were found to be significantly affected by sevoflurane administration. Their target genes clustered into different functional groups, such as ‘dephosphorylation’, ‘vesicle localization’ and the ‘Wnt signaling pathway’. miR-101b-3p was closely related with ‘chromatin binding’ and ‘protein serine/threonine kinase activity’. The most represented pathways for miRNAs included ‘neuroactive ligand-receptor interaction’ (miR-1187), ‘long-term depression’ (miR-425-5p), ‘FoxO signaling pathway’ (miR-425-5p) and the ‘neurotrophin signaling pathway’ (miR-467a-3p). miR-467a-3p (degree=89), miR-101b-3p (degree=59), and miR-1187 (degree=51) were the hub nodes in the miRNA regulatory network. The Wnt signaling pathway, miR-467a-3p, miR-1187 and miR-101b-3p may be therapeutic targets for preventing cognitive impairments induced by sevoflurane.