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.

Whole-transcriptome analysis of aluminum-exposed rat hippocampus and identification of ceRNA networks to investigate neurotoxicity of Al

“…performed RNA sequencing on the hippocampus of mice exposed to sevoflurane, and the results also showed that miR-101b-3p expression was down-regulated, which may be a molecular target to prevent cognitive impairment caused by sevoflurane. 58 The literature also reported that propofol up-regulated the expression of rno-miR-665, thereby inhibiting BCL2L1 and increasing the expression of caspase-3, resulting in neurotoxicity. 59 In the ceRNA networks of DEGs in PI3K-AKT signaling pathway, the novel circRNA rno_circ_0,001,722 and rno-miR-34c-5p are at the core.…”

Overexpression of miR‑133b protects against isoflurane‑induced learning and memory impairment

“…miRNAs have been widely suggested to play important roles in various biological processes, including cell proliferation, apoptosis and differentiation, and neuronal inflammation (10,11). The abnormal expression of miRNAs has been reported to have a regulatory effect on learning and memory function (12,13). For example, in one study, miR-132 expression was shown to be downregulated in the hippocampus of elderly mice compared with younger mice, and in vivo experiments suggested that overexpression of miR-132 may reverse the decline in learning and memory (12).…”