MicroRNA‐27a‐3p suppression of peroxisome proliferator‐activated receptor‐γ contributes to cognitive impairments resulting from sevoflurane treatment

Sevoflurane is the most widely used anaesthetic administered by inhalation. Exposure to sevoflurane in neonatal mice can induce learning deficits and abnormal social behaviours. MicroRNA (miR)-27a-3p, a short, noncoding RNA that functions as a tumour suppressor, is upregulated after inhalation of anaesthetic, and peroxisome proliferator-activated receptor γ (PPARγ) is one of its target genes. The objective of this study was to investigate how the miR-27a-3p–PPARγ interaction affects sevoflurane-induced neurotoxicity. A luciferase reporter assay was employed to identify the interaction between miR-27a-3p and PPARγ. Primary hippocampal neuron cultures prepared from embryonic day 0 C57BL/6 mice, were treated with miR-27a-3p or a PPARγ agonist to determine the effect of miR-27a-3p and PPARγ on sevoflurane-induced cellular damage. Cellular damage was assessed by a flow cytometry assay to detect apoptotic cells, immunofluorescence to detect reactive oxygen species, western blotting to detect NOX1/4 and ELISA to measure inflammatory cytokine levels. In vivo experiments were performed using a sevoflurane-induced anaesthetic mouse model to analyse the effects of miR-27a-3p on neurotoxicity by measuring the number of apoptotic neurons using the TUNEL method, and learning and memory function by employing the Morris water maze test. Our results revealed that PPARγ expression was downregulated by miR-27a-3p following sevoflurane treatment in hippocampal neurons. Downregulation of miR-27a-3p expression decreased sevoflurane-induced hippocampal neuron apoptosis by decreasing inflammation and oxidative stress-related protein expression through the upregulation of PPARγ. In vivo tests further confirmed that inhibition of miR-27a-3p expression attenuated sevoflurane-induced neuronal apoptosis, and learning and memory impairment. Our findings suggest that downregulation of miR-27a-3p expression ameliorated sevoflurane-induced neurotoxicity and learning and memory impairment through the PPAR-γ signalling pathway. MicroRNA-27a-3p may therefore be a potential therapeutic target for preventing or treating sevoflurane-induced neurotoxicity. This article is protected by copyright. All rights reserved.