MiR-125b-5p Inhibitor Might Protect Against Sevoflurane-induced Cognitive Impairments by Targeting LIMK1

Author(s): Jun Xiong, Huijun Wang, Feng Mu, Zhanxue Liu, Yin Bao, Yongxing Sun*.

Journal Name: Current Neurovascular Research

Volume 16 , Issue 4 , 2019

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Abstract:

Purpose: Research has shown that exposure to anesthesia might increase the risks of cognitive impairments and learning difficulties. MiR-125b-5p contributed to anesthesia-induced hippocampal apoptosis. However, the role of miR-125b-5p in sevoflurane-induced cognitive impairments remains unclear.

Methods: Firstly, sevoflurane was used to establish a rat model and cognitive impairment was detected by the Morris water maze (MWM) test. The hippocampus was observed by HE staining. The lentivirus-miR-125b-5p antagomiR was transfected into rats to decrease miR-125b-5p. The interaction between miR-125b-5p and LIM domain kinase 1 (LIMK1) was confirmed by the luciferase reporter assay. The mRNA and expression levels of related genes and mRNA were examined by the Quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) and western blot.

Results: Sevoflurane induced the cognitive dysfunction presenting with longer latency time and few platform crossings in rats. Moreover, miR-125b-5p was observed to be up-regulated in both sevoflurane-anesthesia rats and sevoflurane-treated SH-SY5Y cells. More importantly, a decrease in miR-125b-5p could prevent sevoflurane-induced hippocampal apoptosis and inflammation in rats. Moreover, LIMK1 was the target gene of miR-125b-5p. Interestingly, si-LIMK1 could restore the sevoflurane-induced cell apoptosis in SH-SY5Y cells, which was alleviated by miR-125b-5p inhibitor. Finally, the miR-125b-5p inhibitor shortened the time to find the platform and increased the number of platform crossings compared to sevoflurane-anesthesia rats in the Morris water maze test. At the same time, the expression of LIMK1 was dramatically increased.

Conclusion: Altogether, these findings suggested that miR-125b-5p inhibitor could protect against the sevoflurane-induced cognitive impairments by targeting LIMK1.

Keywords: Sevoflurane, miR-125b-5p, cognitive impairments, LIMK1, Morris Water Maze (MWM), SH-SY5Y.

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VOLUME: 16
ISSUE: 4
Year: 2019
Page: [382 - 391]
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DOI: 10.2174/1567202616666190906145936
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