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MicroRNA-27a-3p suppression of peroxisome proliferator-activated receptor-γ contributes to cognitive impairments resulting from sevoflurane treatment.
J Neurochem. 2017 11; 143(3):306-319.JN

Abstract

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 γ (PPAR-γ) is one of its target genes. The objective of this study was to investigate how the miR-27a-3p-PPAR-γ interaction affects sevoflurane-induced neurotoxicity. A luciferase reporter assay was employed to identify the interaction between miR-27a-3p and PPAR-γ. Primary hippocampal neuron cultures prepared from embryonic day 0 C57BL/6 mice were treated with miR-27a-3p inhibitor or a PPAR-γ agonist to determine the effect of miR-27a-3p and PPAR-γ 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-γ 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-γ. 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-γ signalling pathway. MicroRNA-27a-3p may, therefore, be a potential therapeutic target for preventing or treating sevoflurane-induced neurotoxicity.

Authors+Show Affiliations

Department of Anesthesiology and Critical Care Medicine, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.Department of Anesthesiology and Critical Care Medicine, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.Department of Anesthesiology and Critical Care Medicine, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.Department of Anesthesiology and Critical Care Medicine, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.Department of Anesthesiology and Critical Care Medicine, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.Department of Anesthesiology and Critical Care Medicine, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28881034

Citation

Lv, Xiang, et al. "MicroRNA-27a-3p Suppression of Peroxisome Proliferator-activated Receptor-γ Contributes to Cognitive Impairments Resulting From Sevoflurane Treatment." Journal of Neurochemistry, vol. 143, no. 3, 2017, pp. 306-319.
Lv X, Yan J, Jiang J, et al. MicroRNA-27a-3p suppression of peroxisome proliferator-activated receptor-γ contributes to cognitive impairments resulting from sevoflurane treatment. J Neurochem. 2017;143(3):306-319.
Lv, X., Yan, J., Jiang, J., Zhou, X., Lu, Y., & Jiang, H. (2017). MicroRNA-27a-3p suppression of peroxisome proliferator-activated receptor-γ contributes to cognitive impairments resulting from sevoflurane treatment. Journal of Neurochemistry, 143(3), 306-319. https://doi.org/10.1111/jnc.14208
Lv X, et al. MicroRNA-27a-3p Suppression of Peroxisome Proliferator-activated Receptor-γ Contributes to Cognitive Impairments Resulting From Sevoflurane Treatment. J Neurochem. 2017;143(3):306-319. PubMed PMID: 28881034.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MicroRNA-27a-3p suppression of peroxisome proliferator-activated receptor-γ contributes to cognitive impairments resulting from sevoflurane treatment. AU - Lv,Xiang, AU - Yan,Jia, AU - Jiang,Jue, AU - Zhou,Xuhui, AU - Lu,Yi, AU - Jiang,Hong, Y1 - 2017/10/03/ PY - 2017/03/13/received PY - 2017/08/29/revised PY - 2017/08/31/accepted PY - 2017/9/8/pubmed PY - 2017/11/3/medline PY - 2017/9/8/entrez KW - PPAR-γ KW - anaesthesia KW - cognitive KW - miR-27a-3p KW - sevoflurane SP - 306 EP - 319 JF - Journal of neurochemistry JO - J. Neurochem. VL - 143 IS - 3 N2 - 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 γ (PPAR-γ) is one of its target genes. The objective of this study was to investigate how the miR-27a-3p-PPAR-γ interaction affects sevoflurane-induced neurotoxicity. A luciferase reporter assay was employed to identify the interaction between miR-27a-3p and PPAR-γ. Primary hippocampal neuron cultures prepared from embryonic day 0 C57BL/6 mice were treated with miR-27a-3p inhibitor or a PPAR-γ agonist to determine the effect of miR-27a-3p and PPAR-γ 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-γ 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-γ. 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-γ signalling pathway. MicroRNA-27a-3p may, therefore, be a potential therapeutic target for preventing or treating sevoflurane-induced neurotoxicity. SN - 1471-4159 UR - https://www.unboundmedicine.com/medline/citation/28881034/MicroRNA_27a_3p_suppression_of_peroxisome_proliferator_activated_receptor_γ_contributes_to_cognitive_impairments_resulting_from_sevoflurane_treatment_ L2 - https://doi.org/10.1111/jnc.14208 DB - PRIME DP - Unbound Medicine ER -