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Published on: February 1, 2012
MiR-125b-5p Inhibitor Might Protect Against Sevoflurane-induced Cognitive Impairments by Targeting LIMK1
Jun Xiong1, Huijun Wang2, Feng Mu1
1Department of Anesthesiology, Sanbo Brain Hospital, Capital Medical University, Beijing City, 100093, China.
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.
Insights
Sevoflurane anesthesia can cause cognitive impairment by increasing miR-125b-5p. Inhibiting miR-125b-5p protects against this impairment by targeting LIMK1, improving learning and memory in rats.
Area of Science:
- Neuroscience
- Molecular Biology
- Anesthesiology
Background:
- Anesthesia exposure is linked to cognitive deficits.
- MicroRNA-125b-5p (miR-125b-5p) is implicated in anesthesia-induced hippocampal apoptosis.
- The specific role of miR-125b-5p in sevoflurane-induced cognitive impairment requires elucidation.
Purpose of the Study:
- To investigate the role of miR-125b-5p in sevoflurane-induced cognitive impairments.
- To explore the underlying molecular mechanisms involving LIM domain kinase 1 (LIMK1).
Main Methods:
- Sevoflurane exposure in a rat model to induce cognitive impairment, assessed via Morris water maze (MWM) and HE staining.
- Transfection with lentivirus-miR-125b-5p antagomiR to reduce miR-125b-5p levels.
- Luciferase reporter assay to confirm miR-125b-5p and LIMK1 interaction.
- Quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) and western blot to analyze gene and protein expression.
Main Results:
- Sevoflurane exposure led to cognitive dysfunction and increased miR-125b-5p expression in rats and SH-SY5Y cells.
- Reduced miR-125b-5p expression mitigated sevoflurane-induced hippocampal apoptosis and inflammation.
- LIMK1 was identified as a direct target of miR-125b-5p; its inhibition reversed sevoflurane-induced apoptosis.
- miR-125b-5p inhibition improved MWM performance and increased LIMK1 expression in rats.
Conclusions:
- miR-125b-5p inhibition offers neuroprotection against sevoflurane-induced cognitive impairment.
- The protective effect is mediated through the targeting of LIMK1.
- This study highlights miR-125b-5p as a potential therapeutic target for managing anesthesia-related cognitive side effects.
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