Research Paper Volume 12, Issue 6 pp 5209—5220
MicroRNA-325-3p prevents sevoflurane-induced learning and memory impairment by inhibiting Nupr1 and C/EBPβ/IGFBP5 signaling in rats
- 1 Department of Anesthesiology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
received: November 25, 2019 ; accepted: January 27, 2020 ; published: March 19, 2020 ;https://doi.org/10.18632/aging.102942
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Copyright © 2020 Xu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Endoplasmic reticulum stress-induced neuronal apoptosis contributes to neurotoxicity observed after sevoflurane exposure. However, the molecular mechanism underlying the resulting learning and memory impairments remains unknown. Here, we investigated the roles of miR-325-3p and Nupr1 in sevoflurane-induced learning and memory impairments in neonatal rats and HCN-2 human cortical neuronal cells. We found that in both neonatal rats and HCN-2 cells, sevoflurane exposure impairs learning and memory in neonatal rats and increases expression of Nupr1, the endoplasmic reticulum stress marker proteins C/EBPβ and IGFBP5, and the apoptosis-related protein markers cleaved-Caspase-3 and Bax. Using bioinformatics tools to identify microRNAs that bind to Nupr1, we found that miR-325-3p is downregulated in hippocampal neurons exposed to sevoflurane. Moreover, Nupr1 knockdown and miR-325-3p overexpression improved the rats’ performance in learning and memory tests and reduced sevoflurane-induced apoptosis in vitro and in vivo. These results suggest that miR-325-3p blocks sevoflurane-induced learning and memory impairments by inhibiting Nupr1 and the downstream C/EBPβ/IGFBP5 signaling axis in neonatal rats. MiR-325-3p may therefore be a useful therapeutic target in sevoflurane-induced neurotoxicity.