| First Author | Lv X | Year | 2017 |
| Journal | J Neurochem | Volume | 143 |
| Issue | 3 | Pages | 306-319 |
| PubMed ID | 28881034 | Mgi Jnum | J:245119 |
| Mgi Id | MGI:5915613 | Doi | 10.1111/jnc.14208 |
| Citation | Lv X, et al. (2017) MicroRNA-27a-3p suppression of peroxisome proliferator-activated receptor-gamma contributes to cognitive impairments resulting from sevoflurane treatment. J Neurochem 143(3):306-319 |
| abstractText | 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, non-coding RNA that functions as a tumour suppressor, is up-regulated after inhalation of anaesthetic, and peroxisome proliferator-activated receptor gamma (PPAR-gamma) is one of its target genes. The objective of this study was to investigate how the miR-27a-3p-PPAR-gamma interaction affects sevoflurane-induced neurotoxicity. A luciferase reporter assay was employed to identify the interaction between miR-27a-3p and PPAR-gamma. Primary hippocampal neuron cultures prepared from embryonic day 0 C57BL/6 mice were treated with miR-27a-3p inhibitor or a PPAR-gamma agonist to determine the effect of miR-27a-3p and PPAR-gamma 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 NADPH oxidase 1/4 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 Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL) method and learning and memory function by employing the Morris water maze test. Our results revealed that PPAR-gamma expression was down-regulated by miR-27a-3p following sevoflurane treatment in hippocampal neurons. Down-regulation of miR-27a-3p expression decreased sevoflurane-induced hippocampal neuron apoptosis by decreasing inflammation and oxidative stress-related protein expression through the up-regulation of PPAR-gamma. 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 down-regulation of miR-27a-3p expression ameliorated sevoflurane-induced neurotoxicity and learning and memory impairment through the PPAR-gamma signalling pathway. MicroRNA-27a-3p may, therefore, be a potential therapeutic target for preventing or treating sevoflurane-induced neurotoxicity. |
